Organisms have evolved different strategies to seclude certain molecules to specific locations of the cell. This is most pronounced in eukaryotes with their extensive intracellular membrane systems. Intracellular compartmentalization is particularly critical in genome containing organelles, which because of their bacterial evolutionary ancestry still maintain protein-synthesis machinery that resembles more their evolutionary origin than the extant eukaryotic cell they once joined as an endosymbiont. Despite this, it is clear that genome-containing organelles such as the mitochondria are not in isolation and many molecules make it across the mitochondrial membranes from the cytoplasm. In this realm the import of tRNAs and the enzymes that modify them prove most consequential. In this review, we discuss two recent examples of how modifications typically found in cytoplasmic tRNAs affect mitochondrial translation in organisms that forcibly import all their tRNAs from the cytoplasm. In our view, the combination of tRNA import and the compartmentalization of modification enzymes must have played a critical role in the evolution of the organelle. © 2018 IUBMB Life, 70(12):1207-1213, 2018.

Department of Microbiology Ohio State Biochemistry Program and The Center for RNA Biology The Ohio State University Columbus OH USA

Institute of Parasitology Biology Centre Czech Academy of Sciences and Faculty of Sciences University of South Bohemia České Budějovice Czech Republic

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Alfonzo JD, and Lukeš J (2011) Assembling Fe/S-clusters and modifying tRNAs: Ancient co-factors meet ancient adaptors. Trends Parasitol 27: 235–238. PubMed PMC

Alfonzo JD, and Söll D (2009) Mitochondrial tRNA import--the challenge to understand has just begun. Biol Chem. 390:717–22. PubMed PMC

Benne R, Van den Burg J, Brakenhoff J, Sloof P, Van Boom J, Tromp M (1986) Major transcript of the frameshifted coxII gene from trypanosome mitochondria contains four nucleotides that are not encoded in the DNA Cell 46: 819–826. PubMed

Boccaletto P, Machnicka MA, Purta E, Piątkowski P, Bagiński B, Wirecki TK, de Crécy-Lagard V, Ross R, Limbach PA, Kotter A, Helm M (2017) MODOMICS: a database of RNA modification pathways. 2017 update. Nucleic Acids Research 46: D303–D307. PubMed PMC

Braymer JJ, Lill R (2017) Iron-sulfur cluster biogenesis and trafficking in mitochondria. J Biol Chem. 292:12754–12763. PubMed PMC

Bruske EI, Sendfeld F, and Schneider A (2009) Thiolated tRNAs of Trypanosoma brucei are imported into mitochondria and dethiolated after import. J Biol Chem 284: 36491–36499. PubMed PMC

Charrière F, Helgadóttir S, Horn EK, Söll D, and Schneider A (2006) Dual targeting of a single tRNATrp requires two different tryptophanyl-tRNA synthesis in Typanosoma brucei. Proc Natl Acad Sci U S A 103: 6847–6852. PubMed PMC

Chatterjee K, Nostramo RT, Wan Y, and Hopper AK (2018) tRNA dynamics between the nucleus, cytoplasm and mitochondrial surface: Location, location, location. Biochim Biophys Acta - Gene Regul Mech 1861: 373–386. PubMed PMC

Crain PF, Alfonzo JD, Rozenski J, Kapushoc ST, McCloskey JA, and Simpson L (2002) Modification of the universally unmodified uridine-33 in a mitochondria-imported edited tRNA and the role of the anticodon arm structure on editing efficiency. RNA 8: 752–761. PubMed PMC

de Crécy-Lagard V, Brochier-Armanet C, Urbonavicius J, Fernandez B, Phillips G, Lyons B, Noma A, Alvarez S, Droogmans L, Armengaud J, Grosjean H (2010) Biosynthesis of wyosine derivatives in tRNA: an ancient and highly diverse pathway in Archaea. Mol Biol Evol. 27:2062–77. PubMed PMC

Esseiva AC,Naguleswaran A, Hemphill A, Schneider A (2004) Mitochondrial tRNA import in Toxoplasma gondii. J Biol Chem. 279:42363–8. PubMed

Farabaugh PJ, Björk GR (1999) How translational accuracy influences reading frame maintenance. EMBO J. 18:1427–34. PubMed PMC

Goto-Ito S, Ito T, and Yokoyama S (2017) Trm5 and trmd: Two enzymes from distinct origins catalyze the identical trna modification, m1g37. Biomolecules 7: 1–10. PubMed PMC

Grosjean H, and Westhof E (2016) An integrated, structure- and energy-based view of the genetic code. Nucleic Acids Res. 44: 8020–8040. PubMed PMC

Kamenski P, Kolesnikova O, Jubenot V, Entelis N, Krasheninnikov IA, Martin R, and Tarassov I (2007) Evidence for an Adaptation Mechanism of Mitochondrial Translation via tRNA Import from the Cytosol. Mol Cell 26: 625–637. PubMed

Kaneko T, Suzuki TT, Kapushoc ST, Rubio MA, Ghazvini J, Watanabe K, et al. (2003) Wobble modification differences and subcellular localization of tRNAs in Leishmania tarentolae: implication for tRNA sorting mechanism. EMBO J 22: 657–667. PubMed PMC

Kramer EB, and Hopper AK (2013) Retrograde transfer RNA nuclear import provides a new level of tRNA quality control in Saccharomyces cerevisiae. 1–6. PubMed PMC

Lill R, Srinivasan V, Mühlenhoff U, and Muhlenhoff U (2014) The role of mitochondria in cytosolic-nuclear iron–sulfur protein biogenesis and in cellular iron regulation. Curr Opin Microbiol 22: 111–119. PubMed

Lonhienne TG, Sagulenko E, Webb RI, Lee KC, Franke J, Devos DP, Nouwens A, Carroll BJ, Fuerst JA (2010) Endocytosis-like protein uptake in the bacterium Gemmata obscuriglobus. Proc Natl Acad Sci USA 107:12883–8. PubMed PMC

Lopes RR, Kessler AC, Polycarpo C, Alfonzo JD (2015) Cutting, dicing, healing and sealing: the molecular surgery of tRNA. Wiley Interdiscip Rev RNA 6:337–49. PubMed PMC

Lopes RRS, Silveira GDEO, Eitler R, Vidal RS, Alfonzo JD, Polycarpo C, et al. (2016) The essential function of the Trypanosoma brucei Trl1 homolog in procyclic cells is maturation of the intron-containing tRNA Tyr. RNA 1190–1199. PubMed PMC

Lorenz C, Lünse CE, Mörl M, (2017) tRNA Modifications: Impact on Structure and Thermal Adaptation. Biomolecules 7: 35. PubMed PMC

Michaud M, Cognat V, Duchên AM, Maréchal‐Drouard L (2011) A global picture of tRNA genes in plant genomes. Plant J 66: 80–93. PubMed

Nakai Y, Umeda N, Suzuki T, Nakai M, Hayashi H, Watanabe K, and Kagamiyama H (2004) Yeast Nfs1p Is Involved in Thio-modification of Both Mitochondrial and Cytoplasmic tRNAs. J Biol Chem 279: 12363–12368. PubMed

Noma A, Kirino Y, Ikeuchi Y, and Suzuki T (2006) Biosynthesis of wybutosine, a hyper-modified nucleoside in eukaryotic phenylalanine tRNA. EMBO J 25: 2142–2154. PubMed PMC

Paris Z, Horáková E, Rubio MAT, Sample P, Fleming IMC, Armocida S, et al. (2013) The T. brucei TRM5 methyltransferase plays an essential role in mitochondrial protein synthesis and function. RNA 19. PubMed PMC

Paris Z, Rubio MAT, Lukes J, Alfonzo JD (2009) Mitochondrial tRNA import in Trypanosoma brucei is independent of thiolation and the Rieske protein. RNA 15: 1398–1406. PubMed PMC

Perche-Letuvee P, Molle T, Forouhar F, Mulliez E, and Atta M (2014) Wybutosine biosynthesis: structural and mechanistic overview. RNA Biol 11: 1508–1518. PubMed PMC

Rossignol R, Faustin B, Rocher C, Malgat M, Mazat J, and Letellier T (2003) Mitochondrial threshold effects. 762: 751–762. PubMed PMC

Rubio MAT, Rinehart JJ, Krett B, Duvezin-Caubet SS, Reichert AS, Soll D, et al. (2008) Mammalian mitochondria have the innate ability to import tRNAs by a mechanism distinct from protein import. Proc Natl Acad Sci U S A 105: 9186–91. PubMed PMC

Salinas-Giege T, Giege R, and Giege P (2015) tRNA biology in mitochondria. Int J Mol Sci 16: 4518–4559. PubMed PMC

Sample PJ, Koreny L, Paris Z, Gaston KW, Rubio MAT, Fleming IMC, et al. (2015) A common tRNA modification at an unusual location: the discovery of wyosine biosynthesis in mitochondria. Nucleic Acids Res 43: 4262–4273. PubMed PMC

Shaheen HH, Hopper AK, (2005) Retrograde movement of tRNAs from the cytoplasm to the nucleus in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 102:11290–5. PubMed PMC

Simpson AM, Suyama Y, Dewes H, Campbell DA, Simpson L (1989) Kinetoplastid mitochondria contain functional tRNAs which are encoded in nuclear DNA and also contain small minicircle and maxicircle transcripts of unknown function. Nucleic Acids Res 17:5427–5445. PubMed PMC

Takano A, Endo T, Yoshihisa T (2005) tRNA actively shuttles between the nucleus and cytosol in yeast. Science 309:140–142. PubMed

Wohlgamuth-Benedum JM, Rubio MAT, Paris Z, Long S, Poliak P, Lukes J, and Alfonzo JD (2009) Thiolation controls cytoplasmic tRNA stability and acts as a negative determinant for tRNA editing in mitochondria. J Biol Chem 284: 23947–23953. PubMed PMC

Yoshihisa T, Yunoki-Esaki K, Ohshima C, Tanaka N, and Endo T (2003) Possibility of cytoplasmic pre-tRNA splicing: the yeast tRNA splicing endonuclease mainly localizes on the mitochondria. Mol Biol Cell 14: 3266–3279. PubMed PMC