Protein synthesis is a fundamental biological mechanism bringing the DNA-encoded genetic information into life by its translation into molecular effectors - proteins. The initiation phase of translation is one of the key points of gene regulation in eukaryotes, playing a role in processes from neuronal function to development. Indeed, the importance of the study of protein synthesis is increasing with the growing list of genetic diseases caused by mutations that affect mRNA translation. To grasp how this regulation is achieved or altered in the latter case, we must first understand the molecular details of all underlying processes of the translational cycle with the main focus put on its initiation. In this review I discuss recent advances in our comprehension of the molecular basis of particular initiation reactions set into the context of how and where individual eIFs bind to the small ribosomal subunit in the pre-initiation complex. I also summarize our current knowledge on how eukaryotic initiation factor eIF3 controls gene expression in the gene-specific manner via reinitiation.

Laboratory of Eukaryotic Gene Regulation Institute of Microbiology AS CR Prague Czech Republic

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Sonenberg N, Hinnebusch AG. Regulation of Translation Initiation in Eukaryotes, Mechanisms and Biological Targets. Cell . 2009;136:731–745. PubMed PMC

Pisarev AV, Hellen CUT. Pestova TV Recycling of Eukaryotic Posttermination Ribosomal Complexes. Cell. 2007;131:286–299. PubMed PMC

Pisarev AV, Skabkin MA, Pisareva VP, Skabkina OV, Rakotondrafara AM, Hentze MW, Hellen CU, Pestova TV. The Role of ABCE1 in Eukaryotic Posttermination Ribosomal Recycling. Mol. Cell. 2010;37:196–210. PubMed PMC

Khoshnevis S, Gross T, Rotte C, Baierlein C, Ficner R, Krebber H. The iron-sulphur protein RNase L inhibitor functions in translation termination. EMBO. Rep. 2010;11:214–219. PubMed PMC

Gartmann M, Blau M, Armache JP, Mielke T, Topf M, Beckmann R. Mechanism of eIF6-mediated Inhibition of Ribosomal Subunit Joining. J. Biol. Chem. 2010;285:14848–14851. PubMed PMC

Ceci M, Gaviraghi C, Gorrini C, Sala LA, Offenhauser N, Marchisio PC, Biffo S. Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly. Nature. 2003;426:579–584. PubMed

Klinge S, Voigts-Hoffmann F, Leibundgut M, Arpagaus S, Ban N. Crystal Structure of the Eukaryotic 60S Ribosomal Subunit in Complex with Initiation Factor 6. Science. 2011;334:41–948. PubMed

Hinnebusch AG, Dever TE, Asano KA, Sonenberg N, Mathews M, Hershey JWB. Translational Control in biology and medicine. Cold Spring Harbor: NY., Cold Spring Harbor Laboratory Press,; 2007. Mechanism of translation initiation in the yeast Saccharomyces cerevisiae; pp. 225–268.

Pestova TV, Lorsch JR, Hellen CUT. Translational Control in biology and medicine. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 2007. The mechanism of translation initiation in eukaryotes; pp. 87–128.

Jackson RJ, Hellen CUT, Pestova TV. The mechanism of eukaryotic translation initiation and principles of its regulation. Nat. Rev. Mol. Cell. Biol. 2010;11:113–127. PubMed PMC

Valá??ek L, Nielsen KH, Zhang F, Fekete CA, Hinnebusch AG. Interactions of Eukaryotic Translation Initiation Factor 3 (eIF3) Subunit NIP1/c with eIF1 and eIF5 Promote Preinitiation Complex Assembly and Regulate Start Codon Selection. Mol. Cell. Biol. 2004;24:9437–9455. PubMed PMC

Valá??ek L, Nielsen KH, Hinnebusch AG. Direct eIF2-eIF3 contact in the multifactor complex is important for translation initiation in Vivo. EMBO J. 21:5886–5898. PubMed PMC

Nielsen KH, Szamecz B, Valasek LJA, Shin BS, Hinnebusch AG. Functions of eIF3 downstream of 48S assembly impact AUG recognition and GCN4 translational control. EMBO J. 2004;23:1166–1177. PubMed PMC

Nielsen KH, Valá??ek L, Sykes C, Jivotovskaya A, Hinnebusch AG. Interaction of the RNP1 motif in PRT1 with HCR1 promotes 40S binding of eukaryotic initiation factor 3 in yeast. Mol. Cell. Biol. 2006;26:2984–2998. PubMed PMC

Jivotovskaya A, Valá??ek L, Hinnebusch AG, Nielsen KH. Eukaryotic translation initiation factor 3 (eIF3) and eIF2 can promote mRNA binding to 40S subunits independently of eIF4G in yeast. Mol. Cell. Biol. 2006;26:1355–1372. PubMed PMC

Yamamoto Y, Singh CR, Marintchev A, Hall NS, Hannig EM, Wagner G, Asano K. The eukaryotic initiation factor (eIF) 5 HEAT domain mediates multifactor assembly and scanning with distinct interfaces to eIF1, eIF2, eIF3, and eIF4G. Proc. Natl. Acad. Sci. USA. 2005;102:16164–16169. PubMed PMC

ElAntak L, Wagner S, Herrmannová A, Karásková M, Rutkai E, Lukavsky PJ, Valásek L. The indispensable N-terminal half of eIF3j co-operates with its structurally conserved binding partner eIF3b-RRM and eIF1A in stringent AUG selection. J. Mol. Biol. 2010;396:1097–1116. PubMed PMC

Cuchalová. L. Kouba T, Herrmannová A, Danyi I, Chiu Wl, Valásek L. The RNA Recognition Motif of Eukaryotic Translation Initiation Factor 3g (eIF3g) Is Required for Resumption of Scanning of Posttermination Ribosomes for Reinitiation on GCN4 and Together with eIF3i Stimulates Linear Scanning. Mol. Cell. Biol., 2010;30:4671–4686. PubMed PMC

Chiu WL, Wagner S, Herrmannova A, Burela L, Zhang F, Saini AK, Valásek L, Hinnebusch AG. The C-Terminal Region of Eukaryotic Translation Initiation Factor 3a (eIF3a) Promotes mRNA Recruitment, Scanning, and, Together with eIF3j and the eIF3b RNA Recognition Motif, Selection of AUG Start Codons. Mol. Cell. Biol. 2010;30:4415–4434. PubMed PMC

Mitchell SF, Walker SE, Algire MA, Park EH, Hinnebusch AG, Lorsch JR. The 5'-7-Methylguanosine Cap on Eukaryotic mRNAs Serves Both to Stimulate Canonical Translation Initiation and to Block an Alternative Pathway. Mol. Cell. 2010;39:950–962. PubMed PMC

Dennis MD, Person MD, Browning KS. Phosphorylation of Plant Translation Initiation Factors by CK2 Enhances the in vitro Interaction of Multifactor Complex Components. J. Biol. Chem. 2009;284:20615–20628. PubMed PMC

Sokabe M, Fraser CS, Hershey JWB. The human translation initiation multi-factor complex promotes methionyl-tRNAi binding to the 40S ribosomal subunit. Nucleic Acids Res. 2011;40:905–913. PubMed PMC

Passmore LA, Schmeing TM, Maag D, Applefield DJ, Acker MG, Algire MA, Lorsch JR, Ramakrishnan V. The eukaryotic translation initiation factors eIF1 and eIF1A induce an open conformation of the 40S ribosome. Mol. Cell. 2007;26:41–50. PubMed

LeFebvre AK, Korneeva NL, Trutschl M, Cvek U, Duzan RD, Bradley CA, Hershey JW, Rhoads RE. Translation initiation factor eIF4G-1 binds to eIF3 through the eIF3e subunit. J. Biol. Chem. 2006;281:22917–22932. PubMed PMC

Asano K, Shalev A, Phan L, Nielsen K, Clayton J, et al. Multiple roles for the carboxyl terminal domain of eIF5 in translation initiation complex assembly and GTPase activation. EMO J. 2001;20:2326–2337. PubMed PMC

Hinton TM, Coldwell MJ, Carpenter GA, Morley SJ, Pain VM. Functional analysis of individual binding activities of the scaffold protein eIF4G. J. Biol. Chem. 2007;282:1695–1708. PubMed

Ramirez-Valle F, Braunstein S, Zavadil J, Formenti SC, Schneider RJ. eIF4GI links nutrient sensing by mTOR to Cell, proliferation and inhibition of autophagy. J.Cell Biol. 2008;181: 293–307. PubMed PMC

Park EH, Zhang F, Warringer J, Sunnerhagen P, Hinnebusch AG. Depletion of eIF4G from yeast Cell,s narrows the range of translational efficiencies genome-wide. BMC Genom. 2011;12: 68. PubMed PMC

Clarkson BK, Gilbert WV, Doudna JA. Functional overlap between eIF4G isoforms in Saccharomyces cerevisiae. PLoOne. 2010 ;5:e9114. PubMed PMC

Kozak M. How do eucaryotic ribosomes select initiation regions in messenger RNA? Cell. 1978;15:1109–1123. PubMed

Pestova TV, Kolupaeva VG. The roles of individual eukaryotic translation initiation factors in ribosomal scanning and initiation codon selection. Genes Dev. 2002;16:2906–2922. PubMed PMC

Hinnebusch AG. Molecular Mechanism of Scanning and Start Codon Selection in Eukaryotes. Microbiol. Molecular Biol.Rev. 2011;75:434–467. PubMed PMC

Algire MA, Maag D, Lorsch JR. Pi release from eIF2.; not GTP hydrolysis.; is the step controlled by start-site selection during eukaryotic translation initiation. Mol. Cell . 2005; 20:251–262. PubMed

Maag D, Algire MA, Lorsch JR. Communication between eukaryotic translation initiation factors 5 and 1A within the ribosomal pre-initiation complex plays a role in start site selection. J. Mol. Biol. 2006;356:724–737. PubMed

Saini AK, Nanda JS, Lorsch JR, Hinnebusch AG. Regulatory elements in eIF1A control the fidelity of start codon selection by modulating tRNAiMet binding to the ribosome. Genes Dev. 2010; 24:97–110. PubMed PMC

Cheung YN, Maag D, Mitchell SF, Fekete CA, Algire MA, Takacs JE, Shirokikh N, Pestova T, Lorsch JR, Hinnebusch AG. Dissociation of eIF1 from the 40S ribosomal subunit is a key step in start codon selection in Vivo. Genes Dev. 2007;21: 1217–1230. PubMed PMC

Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986;44:283–292. PubMed

Herrmannová A, Daujotyte D, Yang J-C, Cuchalová L, Gorrec F, Wagner S, Dányi I, Lukavsky PJ, Valásek LS. Structural analysis of an eIF3 subcomplex reveals conserved interactions required for a stable and proper translation pre-Initiation complex assembly. Nucleic Acids Res. 2012;40()(5 ):2294–2311. PubMed PMC

Pestova TV, Lomakin IB, Lee JH, Choi SK, Dever TE, Hellen CU. The joining of ribosomal subunits in eukaryotes requires eIF5B. Nature. 2000;403:332–335. PubMed

Lee JH, Pestova TV, Shin BS, Cao C, Choi SK, Dever TE. Initiation factor eIF5B catalyzes second GTP-dependent step in eukaryotic translation initiation. Proc. Natl. Acad. Sci.USA. 2002;99:16689–16694. PubMed PMC

Szamecz B, Rutkai E, Cuchalova L, Munzarova V, Herrmannova A, et al. eIF3a cooperates with sequences 5' of uORF1 to promote resumption of scanning by post-termination ribosomes for reinitiation on GCN4 mRNA. Genes Dev. 2008;22:2414–2425. PubMed PMC

Munzarová V, Pánek J, Guni??ová S, Dányi I, Szamecz B, Valá??ek LS. Translation Reinitiation Relies on the Interaction between eIF3a/TIF32 and Progressively Folded cis-Acting mRNA Elements Preceding Short uORFs. PLoS Genet. 2011;7:e1002137. PubMed PMC

Pöyry TA, Kaminski A, Jackson RJ. What determines whether mammalian ribosomes resume scanning after translation of a short upstream open reading frame? Genes Dev. 2004;18:62–75. PubMed PMC

Fabian JR, Kimball SR, Heinzinger NK, Jefferson LS. Subunit assembly and guanine nucleotide exchange activity of eukaryotic initiation factor-2B expressed in Sf9 Cell,s. J. Biol. hem. 1997; 272:12359–12365. PubMed

Pavitt GD, Ramaiah KVA, Kimball SR, Hinnebusch AG. eIF2 independently binds two distinct eIF2B subcomplexes that catalyze and regulate guanine-nucleotide exchange. Genes Dev. 1998;12:514–526. PubMed PMC

Singh CR, Lee B, Udagawa T, Mohammad-Qureshi SS, Yamamoto Y, Pavitt GD, Asano K. An eIF5/eIF2 complex antagonizes guanine nucleotide exchange by eIF2B during translation initiation. EMBO J. 2006;25:4537–4546. PubMed PMC

Jennings MD, Pavitt GD. eIF5 has GDI activity necessary for translational control by eIF2 phosphorylation. Nature. 2010;465:378–381. PubMed PMC

Sonenberg N, Mathews M, Hershey JWB, Ron D, Harding HP. Cold Spring Harbor NY Cold: Spring Harbor Laboratory Press.; 2007. eIF2?? phosphorylation in Cellular stress and disease In editors Translational Control in biology and medicine; pp. 345–368.

Schmeing TM, Ramakrishnan V. What recent ribosome structures have revealed about the mechanism of translation. Nature. 2009;461:1234–1242. PubMed

Taylor DJ, Devkota B, Huang AD, Topf M, Narayanan E, Sali A, Harvey SC, Frank J. Comprehensive Molecular Structure of the Eukaryotic Ribosome. Structure. 2009;17:1591–1604. PubMed PMC

Spahn CM, Beckmann R, Eswar N, Penczek PA, Sali A, Blobel G, Frank J. Structure of the 80S ribosome from Saccharomyces cerevisiae - tRNA ribosome and subunit-subunit interactions. Cell. 2001;107:373–386. PubMed

Rabl J, Leibundgut M, Ataide SF, Haag A, Ban N. Crystal Structure of the Eukaryotic 40S Ribosomal Subunit in Complex with Initiation Factor 1. Science. 2011;331:730–736. PubMed

Ben-Shem A, Jenner L, Yusupova G, Yusupov M. Crystal Structure of the Eukaryotic Ribosome. Science. 2010;330:1203–1209. PubMed

Ben-Shem A, Garreau de Loubresse N, Melnikov S, Jenner L, Yusupova G, Yusupov M. The structure of the eukaryotic ribosome at 3. A resolution. Science. 2011;334:1524–1529. PubMed

Takyar S, Hickerson RP, Noller HF. mRNA Helicase Activity of the Ribosome. Cell. 2005;120:49–58. PubMed

Sengupta J, Nilsson J, Gursky R, Spahn CMT, Nissen P, Frank J. Identification of the versatile scaffold protein RACK1 on the eukaryotic ribosome by cryo-EM. Nat. Struct. Mol. Biol. 2004; 11:957–962. PubMed

Nilsson J, Sengupta J, Frank J, Nissen P. Regulation of eukaryotic translation by the RACK1 protein, a platform for signalling molecules on the ribosome. EMBO Rep. 2004;5:1137–1141. PubMed PMC

Liliental J, Chang DD Rack1. a Receptor for Activated Protein Interacts with Integrin ? Subunit. J. Biol. Chem. 1998;273:2379–2383. PubMed

Kouba T, Rutkai E, Karaskova M, Valasek LS. The eIF3c/NIP1 PCI domain interacts with RNA and RACK1/ASC1 and promotes assembly of the pre-initiation complexes. Nucleic Acids Res. 2012;40()(6 ):2683–2699. PubMed PMC

Kiss-László Z, Henry Y, Bachellerie J-P, Caizergues-Ferrer M, Kiss T. Site-Specific Ribose Methylation of Preribosomal RNA, A Novel Function for Small Nucleolar RNAs. Cell. 1996; 85:1077–1088. PubMed

Li Z, Lee I, Moradi E, Hung N-J, Johnson AW, Marcotte EM. Rational Extension of the Ribosome Biogenesis Pathway Using Network-Guided Genetics. PLoS Biol. 2009;7:e1000213. PubMed PMC

Fletcher CM, Pestova TV, Hellen CUT, Wagner G. Structure and interactions of the translation initiation factor eIF1. EMBO J. 1999;18:2631–2639. PubMed PMC

Lomakin IB, Shirokikh NE, Yusupov MM, Hellen CU, Pestova TV. The fidelity of translation initiation, reciprocal activities of eIF1. IF3 and YciH. EMBO J. 2006;25:196–210. PubMed PMC

Lomakin IB, Kolupaeva VG, Marintchev A, Wagner G, Pestova TV. Position of eukaryotic initiation factor eIF1 on the 40S ribosomal subunit determined by directed hydroxyl radical probing. Genes Dev. 2003;17:2786–2797. PubMed PMC

Martin-Marcos P, Cheung YN, Hinnebusch AG. Functional Elements in Initiation Factors 1 1A and 2beta Discriminate against Poor AUG Context and Non-AUG Start Codons. Mol Cell Biol. 2011;31:4814–4831. PubMed PMC

Maag D, Fekete CA, Gryczynski Z, Lorsch JR. A Conformational Change in the Eukaryotic Translation Preinitiation Complex and Release of eIF1 Signal Recognition of the Start Codon. Mol Cell. 2005;7:265–275. PubMed

Unbehaun A, Borukhov SI, Hellen CU, Pestova TV. Release of initiation factors from 48S complexes during ribosomal subunit joining and the link between establishment of codon-anticodon base-pairing and hydrolysis of eIF2-bound GTP. Genes Dev. 2004; 18:3078–3093. PubMed PMC

Nanda JS, Cheung Y-N, Takacs JE, Martin-Marcos P, Saini AK, Hinnebusch AG, Lorsch JR. eIF1 Controls Multiple Steps in Start Codon Recognition during Eukaryotic Translation Initiation. J. Mol. Biol. 2009;394:268–285. PubMed PMC

Conte MR, Kelly G, Babon J, Sanfelice D, Youell J, Smerdon SJ, Proud CG. Structure of the Eukaryotic Initiation Factor (eIF) 5 Reveals a Fold Common to Several Translation Factors. Biochemistry. 2006;45:4550–4558. PubMed

Kolitz SE, Takacs JE, Lorsch JR. Kinetic and thermodynamic analysis of the role of start codon/anticodon base pairing during eukaryotic translation initiation. RNA. 2009;15:138–152. PubMed PMC

Majumdar R, Bandyopadhyay A, Maitra U. Mammalian Translation Initiation Factor eIF1 Functions with eIF1A and eIF3 in the Formation of a Stable 40 S Preinitiation Complex. J. Biol. hem. 2003; 278:6580–6587. PubMed

Ivanov IP, Loughran G, Sachs MS, Atkins JF. Initiation context modulates autoregulation of eukaryotic translation initiation factor 1 (eIF1) Proc. Natl. Acad. Sci. USA. 2010;107:18056–18060. PubMed PMC

Battiste JB, Pestova TV, Hellen CUT, Wagner G. The eIF1A solution structure reveals a large RNA-binding surface important for scanning function. Mol. Cell. 2000;5:109–119. PubMed

Carter AP, Clemons WM, Jr, Brodersen DE, Morgan-Warren RJ, Hartsch T, Wimberly BT, Ramakrishnan V. Crystal structure of an initiation factor bound to the 30S ribosomal subunit. Science. 2001;291:498–501. PubMed

Yu Y. Marintchev A, Kolupaeva VG, Unbehaun A, Veryasova T, Lai SC, Hong P, Wagner G, Hellen CU, Pestova TV. Position of eukaryotic translation initiation factor eIF1A on the 40S ribosomal subunit mapped by directed hydroxyl radical probing. Nucleic Acids Res. 2009;37:5167–5182. PubMed PMC

Olsen DS, Savner EM, Mathew A, Zhang F, Krishnamoorthy T, Phan L, Hinnebusch AG. Domains of eIF1A that mediate binding to eIF2.eIF3 and eIF5B and promote ternary complex recruitment in Vivo. EMBO J. 2003;22:193–204. PubMed PMC

Fekete CA, Applefield DJ, Blakely SA, Shirokikh N, Pestova T, Lorsch JR, Hinnebusch AG. The eIF1A C-terminal domain promotes initiation complex assembly.scanning and AUG selection in Vivo. EMBO J. 2005;24:3588–3601. PubMed PMC

Fekete CA, Mitchell SF, Cherkasova VA, Applefield D, Algire MA, Maag D, Saini AK, Lorsch JR, Hinnebusch AG. N- and C-terminal residues of eIF1A have opposing effects on the fidelity of start codon selection. EMBO J. 2007;26:1602–1614. PubMed PMC

Pestova TV, Borukhov SI, Hellen CUT. Eukaryotic ribosomes require initiation factors 1 and 1A to locate initiation codons. Nature. 1998;394:854–859. PubMed

Erickson FL. Hannig EM. Ligand interactions with eukaryotic translation initiation factor 2, role of the g-subunit. EMBO J. 1996; 15:6311–6320. PubMed PMC

Kapp LD. Lorsch JR. GTP-dependent recognition of the methionine moiety on initiator tRNA by translation factor eIF2. J. Mol. Biol. 2004;335:923–936. PubMed

Krishnamoorthy T, Pavitt GD, Zhang F, Dever TE, Hinnebusch AG. Tight binding of the phosphorylated a subunit of initiation factor 2 (eIF2a) to the regulatory subunits of guanine nucleotide exchange factor eIF2B is required for inhibition of translation initiation. Mol. Cell Biol. 2001;21:5018–5030. PubMed PMC

Farruggio D, Chaudhuri J, Maitra U, RajBhandary UL. The A1 U72 base pair conserved in eukaryotic initiator tRNAs is important specifically for binding to the eukaryotic translation initiation factor eIF2. Mol. Cell Biol. 1996;16:4248–4256. PubMed PMC

von Pawel-Rammingen U, ??ström S, Byström AS. Mutational analysis of conserved positions potentially important for initiator tRNA function in Saccharomyces cerevisiae. Mol. Cell Biol. 1992; 12:1432–1442. PubMed PMC

Dong J, Nanda JS, Rahman H, Pruitt MR, Shin B-S, Wong CM, Lorsch JR, Hinnebusch AG. Genetic identification of yeast 18S rRNA residues required for efficient recruitment of initiator tRNAMet and AUG selection. Genes & Dev. 2008;22:2242–2255. PubMed PMC

Schmitt E, Blanquet S, Mechulam Y. The large subunit of initiation factor aIF2 is a close structural homologue of elongation factors. EMBO J. 2002;21:1821–1832. PubMed PMC

Roll-Mecak A, Cao C, Dever TE, Burley SK. X-Ray structures of the universal translation initiation factor IF2/eIF5B. Conformational changes on GDP and GTP binding. Cell. 2000;103:781–792. PubMed

Nonato MC, Widom J, Clardy J. Crystal structure of the Nterminal segment of human eukaryotic translation initiation factor 2alpha. J. Biol. Chem. 2002;277:17057–17061. PubMed

Stolboushkina E, Nikonov S, Nikulin A, Blasi U, Manstein DJ, Fedorov R, Garber M, Nikonov O. Crystal structure of the intact archaeal translation initiation factor 2 demonstrates very high conformational flexibility in the alpha- and beta-subunits. J. Mol. Biol. 2008;382:680–691. PubMed

Gutierrez P, Osborne MJ, Siddiqui N, Trempe JF, Arrowsmith C, Gehring K. Structure of the archaeal translation initiation factor aIF2 beta from Methanobacterium thermoautotrophicum, implications for translation initiation. Protein. Sci. 2004;3:659–667. PubMed PMC

Dhaliwal S, Hoffman DW. The crystal structure of the Nterminal region of the alpha subunit of translation initiation factor 2 (eIF2alpha) from Saccharomyces cerevisiae provides a view of the loop containing serine 51.the target of the eIF2alpha-specific kinases. J. Mol. Biol. 2003;334:187–195. PubMed

Cho S, Hoffman DW. Structure of the beta subunit of translation initiation factor 2 from the archaeon Methanococcus jannaschii, a representative of the eIF2beta/eIF5 family of proteins. Biochemistry. 2002;41:5730–5742. PubMed

Ito T, Marintchev A, Wagner G. Solution structure of human initiation factor eIF2alpha reveals homology to the elongation factor eEF1B. Structure. 2004;12:1693–1704. PubMed

Yatime L, Mechulam Y, Blanquet S, Schmitt E. Structural switch of the gamma subunit in an archaeal aIF2 alpha gamma heterodimer. Structure. 2006;14:119–128. PubMed

Yatime L, Mechulam Y, Blanquet S, Schmitt E. Structure of an archaeal heterotrimeric initiation factor 2 reveals a nucleotide state between the GTP and the GDP states. Proc. Natl. Acad. Sci. USA. 2007;104:18445–18450. PubMed PMC

Roll-Mecak A, Alone P, Cao C, Dever TE, Burley SK. X-ray structure of translation initiation factor eIF2gamma, implications for tRNA and eIF2alpha binding. J. Biol. Chem. 2004;279:10634–10642. PubMed

Shin B-S, Kim J-R, Walker SE, Dong J, Lorsch JR, Dever TE. Initiation factor eIF2g promotes eIF2-GTP-Met-tRNAiMet ternary complex binding to the 40S ribosome. Nat. Struct. Mol. Biol. 2004;18:1227–1234. PubMed PMC

Alone PV, Dever TE. Direct binding of translation initiation factor eIF2gamma-G domain to its GTPase-activating and GDPGTP exchange factors eIF5 and eIF2B epsilon. J. Biol. hem. 2006;281:12636–12644. PubMed

Alone PV, Cao C, Dever TE. Translation initiation factor 2gamma mutant alters start codon selection independent of MettRNA binding. Mol. Cell. Biol. 2008;28:6877–6888. PubMed PMC

Thompson GM, Pacheco E, Melo EO, Castilho BA. Conserved sequences in the beta subunit of archaeal and eukaryal translation initiation factor 2 (eIF2).; absent from eIF5.; mediate interaction with eIF2gamma. Biochem. J. 2000;347:703–709. PubMed PMC

Das S, Maitra U. Mutational analysis of mammalian translation initiation factor 5 (eIF5), role of interaction between the beta subunit of eIF2 and eIF5 in eIF5 function in vitro and in Vivo. Mol. Cell. Biol. 2000;20:3942–3950. PubMed PMC

Laurino JP, Thompson GM, Pacheco E, Castilho BA. The b subunit of eukaryotic translation initiation factor 2 binds mRNA through the lysine repeats and a region comprising the C2-C2 motif. Molecul. Cell. Biol. 1999;19:173–181. PubMed PMC

Donahue TF, Cigan AM, Pabich EK, Castilho-Valavicius B. Mutations at a Zn(II) finger motif in the yeast elF-2b gene alter ribosomal start-site selection during the scanning process. Cell. . 1988;54:621–632. PubMed

Dever TE, Feng L, Wek RC, Cigan AM, Donahue TF, Hinnebusch AG. Phosphorylation of initiation factor 2a by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast. Cell. 1992;68:585–596. PubMed

Yatime L, Schmitt E, Blanquet S, Mechulam Y. Functional molecular mapping of archaeal translation initiation factor 2. J. Biol. Chem. 2004;279:15984–15993. PubMed

Yatime L, Schmitt E, Blanquet S, Mechulam Y. Structure function relationships of the intact aIF2alpha subunit from the archaeon Pyrococcus abyssi. Biochemistry. 2005;44:8749–8756. PubMed

Pisarev AV, Kolupaeva VG, Pisareva VP, Merrick WC, Hellen CU, Pestova TV. Specific functional interactions of nucleotides at key -3 and +4 positions flanking the initiation codon with components of the mammalian 48S translation initiation complex. Genes. Dev. 2006;20:624–636. PubMed PMC

Masutani M, Sonenberg N, Yokoyama S, Imataka H. Reconstitution reveals the functional core of mammalian eIF3. EMBO. J. 2007;26:3373–3383. PubMed PMC

Zhou M, Sandercock AM, Fraser CS, Ridlova G, Stephens E, Schenauer MR, Yokoi-Fong T, Barsky D, Leary JA, Hershey JW, Doudna JA, Robinson CV. Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3. Proc. Natl. Acad. Sci.USA. 2008;105:18139–18144. PubMed PMC

Sun C, Todorovic A, Querol-Audi J, Bai Y, Villa N, Snyder M, Ashchyan J, Lewis CS, Hartland A, Gradia S, Fraser CS, Doudna JA, Nogales E, Cate JH. Functional reconstitution of human eukaryotic translation initiation factor 3 (eIF3) Proc. Natl. Acad. Sci. 2011;108:20473–20478. PubMed PMC

Valá??ek L, Phan L, Schoenfeld LW, Valá??ková V, Hinnebusch AG. Related eIF3 subunits TIF32 and HCR1 interact with an RNA recoginition motif in PRT1 required for eIF3 integrity and ribosome binding. EMBO J. 2011;20:891–904. PubMed PMC

Asano K, Phan L, Anderson J, Hinnebusch AG. Complex formation by all five homologues of mammalian translation initiation factor 3 subunits from yeast Saccharomyces cerevisiae. J. Biol. Chem. 1998;273:18573–18585. PubMed

Fraser CS, Lee JY, Mayeur GL, Bushell M, Doudna JA, et al. The j-subunit of human translation initiation factor eIF3 is required for the stable binding of eIF3 and its subcomplexes to 40S ribosomal subunits in vitro. J. Biol. Chem. 2004;279:8946–8956. PubMed

ElAntak L, Tzakos AG, Locker N, Lukavsky PJ. Structure of eIF3b RNA recognition motif and its interaction with eIF3j, structural insights into the recruitment of eIF3b to the 40 S ribosomal subunit. J. Biol. Chem. 2007;282:8165–8174. PubMed

Marintchev A, Wagner G. Translation initiation structures. mechanisms and evolution. Q. Rev. Biophys. 2005;37:197–284. PubMed

Asano K, Clayton J, Shalev A, Hinnebusch AG. A multifactor complex of eukaryotic initiation factors eIF1 eIF2 eIF3 eIF5 and initiator tRNAMet is an important translation initiation intermediate in Vivo. Genes Dev. 2000;14:2534–2546. PubMed PMC

Valá??ek L, Mathew A, Shin BS, Nielsen KH, Szamecz B, Hinnebusch AG. The Yeast eIF3 Subunits TIF32/a and NIP1/c and eIF5 Make Critical Connections with the 40S Ribosome in vivo. Genes Dev. 2003;17:786–799. PubMed PMC

Kouba T, Danyi I, Guni??ová S, Munzarová V, Vl??ková V, Cuchalová L, Neueder A, Milkereit P, Valá??ek LS. in press. PLoS ONE: 2012. Small ribosomal protein RPS0 stimulates translation initiation by mediating 40S-binding of eIF3 via its direct contact with the eIF3a/TIF32 subunit. PubMed PMC

Lumsden T, Bentley AA, Beutler W, Ghosh A, Galkin O, Komar AA. Yeast strains with N-terminally truncated ribosomal protein S5, implications for the evolution. structure and function of the Rps5/Rps7 proteins. Nucleic Acids Res. 2010;38:1261–1272. PubMed PMC

Pisarev AV, Kolupaeva VG, Yusupov MM, Hellen CUT, Pestova TV. Ribosomal position and contacts of mRNA in eukaryotic translation initiation complexes. EMBO J. 2008;27:1609–1621. PubMed PMC

Fraser CS, Berry KE, Hershey JW, Doudna JA. 3j is located in the decoding center of the human 40S ribosomal subunit. Mol. Cell. 2007;26:811–819. PubMed

Asano K, Krishnamoorthy T, Phan L, Pavitt GD, Hinnebusch AG. Conserved bipartite motifs in yeast eIF5 and eIF2Be.; GTPase-activating and GDP-GTP exchange factors in translation initiation.; mediate binding to their common substrate eIF2. EMBO J. 1999; 18:1673–1688. PubMed PMC

Siridechadilok B, Fraser CS, Hall RJ, Doudna JA, Nogales E. Structural roles for human translation factor eIF3 in initiation of protein synthesis. Science. 2005;310:1513–1515. PubMed

Asano K, Kinzy TG, Merrick WC, Hershey JWB. Conservation and diversity of eukaryotic translation initiation factor eIF3. J. Biol. Chem. 1997;272:1101–1109. PubMed

Block KL, Vornlocher HP, Hershey JWB. Characterization of cDNAs encoding the p44 and p35 subunits of human translation initiation factor eIF3. J. Biol. Chem. 1998;273:31901–31908. PubMed

Kolupaeva VG, Unbehaun A, Lomakin IB, Hellen CU, Pestova TV. Binding of eukaryotic initiation factor 3 to ribosomal 40S subunits and its role in ribosomal dissociation and antiassociation. RNA. 2005;11:470–486. PubMed PMC

Valá??ek L, Ha??ek J, Trachsel H, Imre EM, Ruis H. The Saccharomyces cerevisiae HCRI gene encoding a homologue of the p35 subunit of human translation eukaryotic initiation factor 3 (eIF3) is a high copy suppressor of a temperature-sensitive mutation in the Rpg1p subunit of yeast eIF3. J. Biol. Chem. 1999;274: 27567–27572. PubMed

Verlhac M-H, Chen R-H, Hanachi P, Hershey JWB, Derynck R. Identification of partners of TIF34.; a component of the yeast eIF3 complex.; required for Cell, proliferation and translation initiation. EMBO J. 1997;16:6812–6822. PubMed PMC

Guo J, Hui DJ, Merrick WC, Sen GC. A new pathway of translational regulation mediated by eukaryotic initiation factor 3. EMBO J. 2000;19:6891–6899. PubMed PMC

Isken O, Kim YK, Hosoda N, Mayeur GL, Hershey JW, Maquat LE. Upf1 Phosphorylation Triggers Translational Repression during Nonsense-Mediated mRNA Decay. Cell. 2008;133:14–327. PubMed PMC

Holz MK, Ballif BA, Gygi SP, Blenis J. mTOR and S6K1 Mediate Assembly of the Translation Preinitiation Complex through Dynamic Protein Interchange and Ordered Phosphorylation Events. Cell. 2005;123:569–580. PubMed

Harris TE, Chi A, Shabanowitz J, Hunt DF, Rhoads RE, Lawrence JC., Jr mTOR-dependent stimulation of the association of eIF4G and eIF3 by insulin. EMBO J. 2006;25:1659–1668. PubMed PMC

Park HS, Himmelbach A, Browning KS, Hohn T, Ryabova LA. A plant viral "reinitiation" factor interacts with the host translational machinery. Cell. 2001;106:723–733. PubMed

Pöyry TA, Kaminski A, Connell EJ, Fraser CS, Jackson RJ. The mechanism of an exceptional case of reinitiation after translation of a long ORF reveals why such events do not generally occur in mammalian mRNA translation. Genes Dev. 2007;21:3149–3162. PubMed PMC

Hellen CUT. IRES-induced conformational changes in the ribosome and the mechanism of translation initiation by internal ribosomal entry. Biochimica et Biophysica Acta (BBA) - Gene Regulat. Mechan. 2009;789:558–570. PubMed PMC

Ryabova LA, Pooggin MM, Hohn T. Viral strategies of translation initiation, ribosomal shunt and reinitiation. Prog. Nucleic Acid Res. Mol. Biol. 2002;72:1–39. PubMed PMC

Hinnebusch AG. Translational regulation of GCN4 and the general amino acid control of yeast. Annu. Rev. Microbiol. 2005;59:407–450. PubMed

Hood HM, Neafsey DE, Galagan J, Sachs MS. Evolutionary Roles of Upstream Open Reading Frames in Mediating Gene Regulation in Fungi. Ann. Rev. Microbiol. 2009;63:385–409. PubMed

Powell ML. Translational termination-reinitiation in RNA viruses. Biochem. Soc. Trans. 2010;38:1558–1564. PubMed

Jackson RJ, Hellen CU, Pestova TV. Termination and posttermination events in eukaryotic translation. Adv. Protein Chem. Struct. Biol. 2012;86:45–93. PubMed

Kozak M. Regulation of translation via mRNA structure in prokaryotes and eukaryotes. Gene. 2005;361:13–37. PubMed

Rajkowitsch L, Vilela C, Berthelot K, Ramirez CV, McCarthy JE. Reinitiation and recycling are distinct processes occurring downstream of translation termination in yeast. J. Mol. Biol. 2004;335:71–85. PubMed

Kozak M. Constraints on reinitiation of translation in mammals. Nucleic Acids Res. 2001;29:5226–5232. PubMed PMC

Grant CM, Hinnebusch AG. Effect of sequence context at stop codons on efficiency of reinitiation in GCN4 translational control. Mol. Cell Biol. 1994;14:606–618. PubMed PMC

Vilela C, Linz B, Rodrigues-Pousada C, McCarthy JE. The yeast transcription factor genes YAP1 and YAP2 are subject to differential control at the levels of both translation and mRNA stability. Nucleic Acids Res. 1998;26:1150–1159. PubMed PMC

Vattem KM, Wek RC. Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian Cells. Proc. Natl. Acad. Sci. USA. 2004;101:11269–11274. PubMed PMC

Zhou D, Pallam LR, Jiang L, Narasimhan J, Staschke KA, Wek RC. Phosphorylation of eIF2 directs ATF5 translational control in response to diverse stress conditions. J. Biol. Chem. 2008; 283:7064–7073. PubMed

Luttermann C, Meyers G. The importance of inter- and intramolecular base pairing for translation reinitiation on a eukaryotic bicistronic mRNA. Genes Dev. 2009;23:331–344. PubMed PMC

Imataka H, Gradi A, Sonenberg N. A newly identified Nterminal amino acid sequence of human eIF4G binds poly (A)- binding protein and functions in poly(A)-dependent translation. EMBO J. 1998;7:7480–7489. PubMed PMC

Imataka H, Olsen S, Sonenberg N. A new translational regulator with homology to eukaryotic translation initiation factor 4G. EMBO J. 1997;16:817–825. PubMed PMC

Imataka H, Sonenberg N. Human eukaryotic translation initiation factor 4G (eIF4G) possesses two separate and independent binding sites for eIF4A. Mol. Cell Biol. 1997;17:6940–6947. PubMed PMC

Korneeva NL, Lamphear BJ, Hennigan FL, Merrick WC, Rhoads RE. Characterization of the two eIF4A-binding sites on human eIF4G-1. J. Biol. Chem. 2001;276:2872–2879. PubMed

Lamphear BJ, Kirchweger R, Skern T, Rhoads RE. Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. J. Biol. Chem. 1995; 270:21975–21983. PubMed

Morino S, Imataka H, Svitkin YV, Pestova TV, Sonenberg N. Eukaryotic translation initiation factor 4E (eIF4E) binding site and the middle one-third of eIF4GI constitute the core domain for cap-dependent translation.and the C-terminal one-third functions as a modulatory region. Mol. Cell Biol. 2000;20:468–477. PubMed PMC

Groft CM, Burley SK. Recognition of eIF4G by rotavirus NSP3 reveals a basis for mRNA circularization. Mol Cell. 2002;9:1273–1283. PubMed

Gross JD, Moerke NJ, von der Haar T, Lugovskoy AA, Sachs AB, McCarthy JE, Wagner G. Ribosome loading onto the mRNA cap is driven by conformational coupling between eIF4G and eIF4E. Cell. 2003;115:739–750. PubMed

Marcotrigiano J, Lomakin IB, Sonenberg N, Pestova TV, Hellen CUT, Burley SK. A conserved HEAT domain within eIF4G directs assembly of the translation initiation machinery. Mol. Cell. 2001;7:193–203. PubMed

Bellsolell L, Cho-Park PF, Poulin F, Sonenberg N, Burley SK. Two structurally atypical HEAT domains in the C-terminal portion of human eIF4G support binding to eIF4A and Mnk1. Structure. 2006;14:913–923. PubMed

Yanagiya A, Svitkin YV, Shibata S, Mikami S, Imataka H, Sonenberg N. Requirement of RNA binding of mammalian eukaryotic translation initiation factor 4GI (eIF4GI) for efficient interaction of eIF4E with the mRNA cap. Mol. Cell Biol. 2009;29:661–1669. PubMed PMC

Park E-H, Walker SE, Lee JM, Rothenburg S, Lorsch JR, Hinnebusch AG. Multiple elements in the eIF4G1 N-terminus promote assembly of eIF4G1[bull]PABP mRNPs in Vivo. EMBO J. 2010;30:302–316. PubMed PMC

Berset C, Zurbriggen A, Djafarzadeh S, Altmann M, Trachsel H. RNA-binding activity of translation initiation factor eIF4G1 from Saccharomyces cerevisiae. RNA. 2003;9:871–880. PubMed PMC

Svitkin YV, Evdokimova VM, Brasey A, Pestova TV, Fantus D, Yanagiya A, Imataka H, Skabkin MA, Ovchinnikov LP, Merrick WC, Sonenberg N. General RNA-binding proteins have a function in poly(A)-binding protein-dependent translation. EMBO J. 2009;28:58–68. PubMed PMC

Tarun SZ, Wells SE, Deardorff JA, Sachs AB. Translation initiation factor eIF4G mediates in vitro poly (A) tail-dependent translation. Proc. Nat. Acad. Sci. USA. 1997;94:9046–9051. PubMed PMC

Marcotrigiano J, Gingras AC, Sonenberg N, Burley SK. Cocrystal structure of the messenger RNA 5' cap-binding protein (eIF4E) bound to 7-methyl-GDP. Cell. 1997;89:951–961. PubMed

Matsuo H, Li H, McGuire AM, Fletcher CM, Gingras A-C, Sonenberg N, Wagner G. Structure of translation factor eIF4E bound to m7GDP and interaction with 4E-binding protein. Nat. Struct. Biol. 1997;4:717–724. PubMed

Haghighat A, Sonenberg N. eIF4G dramatically enhances the binding of eIF4E to the mRNA 5'-cap structure. J. Biol. chem. 1997;272:21677–21680. PubMed

Hershey PEC, McWhirter SM, Gross J, Wagner G, Alber T, Sachs AB. The cap binding protein eIF4E promotes folding of a functional domain of yeast translation initiation factor eIF4G1. J. Biol. Chem. 1999;274:21297–21304. PubMed

von Der Haar T, Ball PD, McCarthy JE. Stabilization of eukaryotic initiation factor 4E binding to the mRNA 5'-Cap by domains of eIF4G. J. Biol. Chem. 2000;275:30551–30555. PubMed

Friedland DE, Wooten WN, LaVoy JE, Hagedorn CH, Goss DJ. A mutant of eukaryotic protein synthesis initiation factor eIF4E(K119A) has an increased binding affinity for both m7G cap analogues and eIF4G peptides. Biochemistry. 2005;44:4546–4550. PubMed

Rhoads RE. eIF4E, new family members.new binding parters.new roles. J. Biol. Chem. 2009;284:16711–16715. PubMed PMC

Mader S, Lee H, Pause A, Sonenberg N. he translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4g and the translational repressors 4E-binding proteins. Mol. Cell Biol. 1995;15:4990–4997. PubMed PMC

Gingras A-C, Raught B, Gygi SP, Niedzwiecka A, Miron M, Burley SK, Polakiewicz RD, Wyslouch-Cieszynska A, Aebersold R, Sonenberg N. Hierarchical phosphorylation of the translation inhibitor 4E-BP1. Genes Dev. 2001;15:2852–2864. PubMed PMC

Gingras A-C, Raught B, Sonenberg N. Regulation of translation initiation by FRAP/mTOR. Genes Dev. 2001;15:807–826. PubMed

Caruthers JM, Johnson ER, McKay DB. Crystal structure of yeast initiation factor 4A. a DEAD-box RNA helicase. Proc. Natl. Acad. Sci. USA. 2000;97:13080–13085. PubMed PMC

Linder P, Jankowsky E. From unwinding to clamping - the DEAD box RNA helicase family. Nat. Rev. Mol. Cell Biol. 2011; 12:505–516. PubMed

Liu F, Putnam A, Jankowsky E. ATP hydrolysis is required for DEAD-box protein recycling but not for duplex unwinding. Proc. Natl. Acad. Sci. USA. 2008;105:20209–20214. PubMed PMC

Dominguez D, Altmann M, Benz J, Baumann U, Trachsel H. Interaction of translation initiation factor eIF4G with eIF4A in the yeast Saccharomyces cerevisiae. J. Biol. Chem. 1999;274:26720–26726. PubMed

Dominguez D, Kislig E, Altmann M, Trachsel H. Structural and functional similarities between the central eukaryotic initiation factor (eIF)4A-binding domain of mammalian eIF4G and the eIF4A-binding domain of yeast eIF4G. Biochem. J. 2001;355: 223–230. PubMed PMC

Neff CL, Sachs AB. Eukaryotic translation initiation factors eIF4G and eIF4A from Saccharomyces cerevisiae physically and functionally interact. Mol. Cell. Biol. 1999;19:5557–5564. PubMed PMC

Pause A, Methot N, Svitkin Y, Merrick WC, Sonenberg N. Dominant negative mutants of mammalian translation initiation factor eIF-4A define a critical role for eIF-4F in cap-dependent and cap-independent initiation of translation. EMBO J. 1994;13:1205–1215. PubMed PMC

Rozen F, Edery I, Meerovitch K, Dever TE, Merrick WC, Sonenberg N. Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F. Mol. Cell Biol. 1990;10:1134–1144. PubMed PMC

Rogers GW, Jr, Richter NJ, Lima WF, Merrick WC. Modulation of the helicase activity of eIF4A by eIF4B. eF4H.and eIF4F. J. Biol. Chem. 2001; 276:30914–30922. PubMed

Richter NJ, Rogers GW, Jr, Hensold JO, Merrick WC. Further biochemical and kinetic characterization of human eukaryotic initiation factor 4H. J. Biol. Chem. 1999;274:35415–35424. PubMed

Rogers GW, Jr, Richter NJ, Merrick WC. Biochemical and kinetic characterization of the RNA helicase activity of eukaryotic initiation factor 4A. J. Biol. Chem. 1999;274:12236–12244. PubMed

Oberer M, Marintchev A, Wagner G. Structural basis for the enhancement of eIF4A helicase activity by eIF4G. Genes Dev. 2005;19:2212–2223. PubMed PMC

Schutz P, Bumann M, Oberholzer AE, Bieniossek C, Trachsel H, Altmann M, Baumann U. Crystal structure of the yeast eIF4A-eIF4G complex, an RNA-helicase controlled by proteinprotein interactions. Proc. Natl. Acad. Sci. USA. 2008;105:9564–9569. PubMed PMC

Feng P, Everly DN, Jr, Read GS. mRNA decay during herpes simplex virus (HSV) infections, protein-protein interactions involving the HSV virion host shutoff protein and translation factors eIF4H and eIF4A. J. Virol. 2005;79:9651–9664. PubMed PMC

Rozovsky N, Butterworth AC, Moore MJ. Interactions between eIF4AI and its accessory factors eIF4B and eIF4H. RNA . 2008;14:2136–2148. PubMed PMC

Marintchev A, Edmonds KA, Marintcheva B, Hendrickson E, Oberer M, Suzuki C, Herdy B, Sonenberg N, Wagner G. Topology and Regulation of the Human eIF4A/4G/4H Helicase Complex in Translation Initiation. Cell. 2009;136:447–460. PubMed PMC

Nielsen KH, Behrens MA, He Y, Oliveira CL, Jensen LS, Hoffmann SV, Pedersen JS, Andersen GR. Synergistic activation of eIF4A by eIF4B and eIF4G. Nucleic Acids Res. 39:2678–2689. PubMed PMC

Bi X, Ren J, Goss DJ. Wheat germ translation initiation factor eIF4B affects eIF4A and eIFiso4F helicase activity by increasing the ATP binding affinity of eIF4A. Biochemistry. 2000;39:5758–5765. PubMed

Niederberger N, Trachsel H, Altmann M. The RNA recognition motif of yeast translation initiation factor Tif3/eIF4B is required but not sufficient for RNA strand-exchange and translational activity. RNA. 1998;4:1259–1267. PubMed PMC

Coppolecchia R, Buser P, Stotz A, Linder P. A new yeast translation initiation factor suppresses a mutation in the eIF-4A RNA helicase. EMBO J. 1993;2:4005–4011. PubMed PMC

Altmann M, Muller PP, Wittmer B, Ruchti F, Lanker S, Ruchti F, Lanker S, Trachsel H. A Saccharomyces cerevisiae homologue of mammalian translation initiation factor 4B contributes to RNA helicase activity. EMBO J. 1993;12:3997–4003. PubMed PMC

Kahvejian A, Svitkin YV, Sukarieh R, M'Boutchou MN, Sonenberg N. Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor.which acts via multiple mechanisms. Genes Dev. 2005;19:104–113. PubMed PMC

Tarun SZ, Sachs AB. Association of the yeast poly(A) tail binding protein with translation initiation factor eIF-4G. EM O J. 1996;15:7168–7177. PubMed PMC

Gray NK, Coller JM, Dickson KS, Wickens M. Multiple portions of poly(A)-binding protein stimulate translation in Vivo. EMBO J. 2000;19:4723–4733. PubMed PMC

Amrani N, Ghosh S, Mangus DA, Jacobson A. Translation factors promote the formation of two states of the closed-loop mRNP. Nature. 2008;453:1276–1280. PubMed PMC

Duncan KE, Strein C, Hentze MW. The SXL-UNR corepressor complex uses a PABP-mediated mechanism to inhibit ribosome recruitment to msl-2 mRNA. Mol. Cell. 2009;36:571–582. PubMed

Yu Y, Abaeva IS, Marintchev A, Pestova TV, Hellen CU. Common conformational changes induced in type 2 picornavirus IRESs by cognate trans-acting factors. Nucleic Acids Res. 2011; 39:4851–4865. PubMed PMC

Maiti T, Maitra U. Characterization of translation initiation factor 5 (eIF5) from Saccharomyces cerevisiae. J. Biol. Chem. 1997;272:833–18340. PubMed

Majumdar R, Maitra U. Regulation of GTP hydrolysis prior to ribosomal AUG selection during eukaryotic translation initiation. EMBO J. 2005;24:3737–3746. PubMed PMC

Das S, Ghosh R, Maitra U. Eukaryotic translation initiation factor 5 functions as a GTPase- activating protein. J. Biol. chem. 2001;276:6720–6726. PubMed

Paulin FE, Campbell LE, O'Brien K, Loughlin J, Proud CG. Eukaryotic translation initiation factor 5 (eIF5) acts as a classical GTPase-activator protein. Curr. Biol. 2001;11:55–59. PubMed

Das S, Maiti T, Das K, Maitra U. Specific interaction of eukaryotic translation initiation factor 5 (eIF5) with the b-subunit of eIF2. J. Biol. Chem. 1997;272:31712–31718. PubMed

Bieniossek C, Schutz P, Bumann M, Limacher A, Uson I, Limacher A, Uson I, Baumann U. The crystal structure of the carboxy-terminal domain of human translation initiation factor eIF5. J. Mol. Biol. 2006;360:457–465. PubMed

Wei Z, Xue Y, Xu H, Gong W. Crystal structure of the Cterminal domain of S.erevisiae eIF5. J. Mol. Biol. 2006;359:1–9. PubMed

Boesen T, Mohammad SS, Pavitt GD, Andersen GR. Structure of the catalytic fragment of translation initiation factor 2B and identification of a critically important catalytic residue. J. Biol. Chem. 2004;279:10584–10592. PubMed

Loughran G, Sachs MS, Atkins JF, Ivanov IP. Stringency of start codon selection modulates autoregulation of translation initiation factor eIF5. Nucleic Acids Res. 2011;40()(7 ):2898–906. PubMed PMC

Fringer JM, Acker MG, Fekete CA, Lorsch JR, Dever TE. Coupled release of eukaryotic translation initiation factors 5B and 1A from 80S ribosomes following subunit joining. Mol. Cell iol. 2007; 27:2384–2397. PubMed PMC

Unbehaun A, Marintchev A, Lomakin IB, Didenko T, Wagner G, Hellen CUT, Pestova TV. Position of eukaryotic initiation factor eIF5B on the 80S ribosome mapped by directed hydroxyl radical probing. EMBO J. 2007;26: 3109–3123. PubMed PMC

Choi SK, Lee JH, Zoll WL, Merrick WC, Dever TE. Promotion of Met-tRNAi Met binding to ribosomes by yIF2.a bacterial IF2 homolog in yeast. Science. 1998;280:1757–1760. PubMed

Terenin IM, Dmitriev SE, Andreev DE, Shatsky IN. Eukaryotic translation initiation machinery can operate in a bacteriallike mode without eIF2. Nat. Struct. Mol. Biol. 2008;15:836–841. PubMed

Laalami S, Putzer H, Plumbridge JA, Grunberg-Manago M. A severely truncated form of translation initiation factor 2 supports growth of Escherichia coli. J. Mol. Biol. 1991;220:335–349. PubMed

Shin BS, Maag D, Roll-Mecak A, Arefin MS, Burley SK, Lorsch JR, Dever TE. Uncoupling of initiation factor eIF5B/IF2 GTPase and translational activities by mutations that lower ribosome affinity. Cell. 2002;111:1015–1025. PubMed

Allen GS, Zavialov A, Gursky R, Ehrenberg M, Frank J. The cryo-EM structure of a translation initiation complex from Escherichia coli. Cell. 2005;121:703–712. PubMed

Simonetti A, Marzi S, Myasnikov AG, Fabbretti A, Yusupov M, Fabbretti A, Yusupov M, Gualerzi CO, Klaholz BP. Structure of the 30S translation initiation complex. Nature. 2008; 455:416–420. PubMed

Choi SK, Olsen DS, Roll-Mecak A, Martung A, Remo KL, Burley SK, Hinnebusch AG, Dever TE. Physical and functional interaction between the eukaryotic orthologs of prokaryotic translation initiation factors IF1 and IF2. Mol. Cell Biol. 2000;20: 7183–7191. PubMed PMC

Acker MG, Shin BS, Nanda JS, Saini AK, Dever TE, Lorsch JR. Kinetic analysis of late steps of eukaryotic translation initiation. J. Mol. Biol. 2009;385:491–506. PubMed PMC

Acker MG, Shin BS, Dever TE, Lorsch JR. Interaction between eukaryotic initiation factors 1A and 5B is required for efficient ribosomal subunit joining. J. Biol. Chem. 2006;281:8469–8475. PubMed

Ingolia NT, Ghaemmaghami S, Newman JRS, Weissman JS. Genome-Wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling. Science. 2009;324:218–223. PubMed PMC

Petrov A, Kornberg G, O'Leary S, Tsai A, Uemura S, Puglisi JD. Dynamics of the translational machinery. Curr. Opinion Struct. Biol. 2011;21:137–145. PubMed PMC

Perturbations in eIF3 subunit stoichiometry alter expression of ribosomal proteins and key components of the MAPK signaling pathways

Differential effects of 40S ribosome recycling factors on reinitiation at regulatory uORFs in GCN4 mRNA are not dictated by their roles in bulk 40S recycling

Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control

Impacts of yeast Tma20/MCTS1, Tma22/DENR and Tma64/eIF2D on translation reinitiation and ribosome recycling

eIF4G is retained on ribosomes elongating and terminating on short upstream ORFs to control reinitiation in yeast

Structural Differences in Translation Initiation between Pathogenic Trypanosomatids and Their Mammalian Hosts

Selective Translation Complex Profiling Reveals Staged Initiation and Co-translational Assembly of Initiation Factor Complexes

uS3/Rps3 controls fidelity of translation termination and programmed stop codon readthrough in co-operation with eIF3

Binding of eIF3 in complex with eIF5 and eIF1 to the 40S ribosomal subunit is accompanied by dramatic structural changes

Dynamics of the Pollen Sequestrome Defined by Subcellular Coupled Omics

Please do not recycle! Translation reinitiation in microbes and higher eukaryotes

Does eIF3 promote reinitiation after translation of short upstream ORFs also in mammalian cells?

Embraced by eIF3: structural and functional insights into the roles of eIF3 across the translation cycle

ABCE1: A special factor that orchestrates translation at the crossroad between recycling and initiation

In vivo evidence that eIF3 stays bound to ribosomes elongating and terminating on short upstream ORFs to promote reinitiation

Human eIF3b and eIF3a serve as the nucleation core for the assembly of eIF3 into two interconnected modules: the yeast-like core and the octamer

Eukaryotic translation initiation factor 3 plays distinct roles at the mRNA entry and exit channels of the ribosomal preinitiation complex

In-depth analysis of cis-determinants that either promote or inhibit reinitiation on GCN4 mRNA after translation of its four short uORFs

Rules of UGA-N decoding by near-cognate tRNAs and analysis of readthrough on short uORFs in yeast

Translation initiation factor eIF3 promotes programmed stop codon readthrough