During the first step of gene expression, RNA polymerase (RNAP) engages DNA to transcribe RNA, forming highly stable complexes. These complexes need to be dissociated at the end of transcription units or when RNAP stalls during elongation and becomes an obstacle ('sitting duck') to further transcription or replication. In this review, we first outline the mechanisms involved in these processes. Then, we explore in detail the torpedo mechanism whereby a 5'-3' RNA exonuclease (torpedo) latches itself onto the 5' end of RNA protruding from RNAP, degrades it and upon contact with RNAP, induces dissociation of the complex. This mechanism, originally described in Eukaryotes and executed by Xrn-type 5'-3' exonucleases, was recently found in Bacteria and Archaea, mediated by β-CASP family exonucleases. We discuss the mechanistic aspects of this process across the three kingdoms of life and conclude that 5'-3' exoribonucleases (β-CASP and Xrn families) involved in the ancient torpedo mechanism have emerged at least twice during evolution.

Centre for Bacterial Cell Biology Biosciences Institute Newcastle University Newcastle upon Tyne NE2 4AX UK

Department of Microbial Genetics and Gene Expression Institute of Microbiology Czech Academy of Sciences Prague CZ 14220 Czech Republic

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Barvík I., Rejman D., Panova N., Šanderová H., Krásný L.. Non-canonical transcription initiation: the expanding universe of transcription initiating substrates. FEMS Microbiol. Rev. 2017; 41:131–138. PubMed

Edenberg E.R., Downey M., Toczyski D. Polymerase stalling during replication, transcription and translation. Curr. Biol. 2014; 24:445–452. PubMed

Shearwin K.E., Callen B.P., Egan J.B.. Transcriptional interference - a crash course. Trends Genet. 2005; 21:339–345. PubMed PMC

García-Muse T., Aguilera A.. Transcription-replication conflicts: how they occur and how they are resolved. Nat. Rev. Mol. Cell Biol. 2016; 17:553–563. PubMed

Merrikh H., Zhang Y., Grossman A.D., Wang J.D.. Replication-transcription conflicts in bacteria. Nat. Rev. Microbiol. 2012; 10:449–458. PubMed PMC

Gómez-González B., Aguilera A.. Transcription-mediated replication hindrance: a major driver of genome instability. Genes Dev. 2019; 33:1008–1026. PubMed PMC

Kang W., Ha K.S., Uhm H., Park K., Lee J.Y., Hohng S., Kang C.. Transcription reinitiation by recycling RNA polymerase that diffuses on DNA after releasing terminated RNA. Nat. Commun. 2020; 11:450. PubMed PMC

Nudler E., Avetissova E., Markovtsov V., Goldfarb A.. Transcription processivity: protein-DNA interactions holding together the elongation complex. Science. 1996; 273:211–217. PubMed

Wilson K.S., Von Hippel P.H. Stability of Escherichia coli transcription complexes near an intrinsic terminator. J. Mol. Biol. 1994; 244:36–51. PubMed

Chen H., Shiroguchi K., Ge H., Xie X.S.. Genome-wide study of mRNA degradation and transcript elongation in Escherichia coli. Mol. Syst. Biol. 2015; 11:781. PubMed PMC

Larson M.H., Mooney R.A., Peters J.M., Windgassen T., Nayak D., Gross C.A., Block S.M., Greenleaf W.J., Landick R., Weissman J.S.. A pause sequence enriched at translation start sites drives transcription dynamics in vivo. Science. 2014; 344:1042–1047. PubMed PMC

Saba J., Chua X.Y., Mishanina T. V., Nayak D., Windgassen T.A., Mooney R.A., Landick R.. The elemental mechanism of transcriptional pausing. Elife. 2019; 8:e40981. PubMed PMC

Perdue S.A., Roberts J.W.. A backtrack-inducing sequence is an essential component of Escherichia coli σ70-dependent promoter-proximal pausing. Mol. Microbiol. 2010; 78:636–650. PubMed PMC

Imashimizu M., Takahashi H., Oshima T., McIntosh C., Bubunenko M., Court D.L., Kashlev M.. Visualizing translocation dynamics and nascent transcript errors in paused RNA polymerases in vivo. Genome Biol. 2015; 16:98. PubMed PMC

Lass-Napiorkowska A., Heyduk T.. Real-time observation of backtracking by bacterial RNA polymerase. Biochemistry. 2016; 55:647–658. PubMed PMC

Dutta D., Shatalin K., Epshtein V., Gottesman M.E., Nudler E.. Linking RNA polymerase backtracking to genome instability in E. coli. Cell. 2011; 146:533–543. PubMed PMC

Churchman L.S., Weissman J.S.. Nascent transcript sequencing visualizes transcription at nucleotide resolution. Nature. 2011; 469:368–373. PubMed PMC

Walter W., Kireeva M.L., Studitsky V.M., Kashlev M.. Bacterial polymerase and yeast polymerase II use similar mechanisms for transcription through nucleosomes. J. Biol. Chem. 2003; 278:36148–36156. PubMed

Nudler E. RNA polymerase backtracking in gene regulation and genome instability. Cell. 2012; 149:1438–1445. PubMed PMC

Lisica A., Engel C., Jahnel M., Roldán É., Galburt E.A., Cramer P., Grill S.W.. Mechanisms of backtrack recovery by RNA polymerases i and II. Proc. Natl. Acad. Sci. U.S.A. 2016; 113:2946–2951. PubMed PMC

Depken M., Galburt E.A., Grill S.W.. The origin of short transcriptional pauses. Biophys. J. 2009; 96:2189–2193. PubMed PMC

Galburt E.A., Grill S.W., Wiedmann A., Lubkowska L., Choy J., Nogales E., Kashlev M., Bustamante C.. Backtracking determines the force sensitivity of RNAP II in a factor-dependent manner. Nature. 2007; 446:820–823. PubMed

Lange U., Hausner W.. Transcriptional fidelity and proofreading in Archaea and implications for the mechanism of TFS-induced RNA cleavage. Mol. Microbiol. 2004; 52:1133–1143. PubMed

Archambault J., Lacroute F., Ruet A., Friesen J.D.. Genetic interaction between transcription elongation factor TFIIS and RNA polymerase II. Mol. Cell. Biol. 1992; 12:4142–4152. PubMed PMC

Jeon C.J., Agarwal K.. Fidelity of RNA polymerase II transcription controlled by elongation factor TFIIS. Proc. Natl. Acad. Sci. USA. 1996; 93:13677–13682. PubMed PMC

Kuhn C.D., Geiger S.R., Baumli S., Gartmann M., Gerber J., Jennebach S., Mielke T., Tschochner H., Beckmann R., Cramer P.. Functional Architecture of RNA Polymerase I. Cell. 2007; 131:1260–1272. PubMed

Ruan W., Lehmann E., Thomm M., Kostrewa D., Cramer P.. Evolution of two modes of intrinsic RNA polymerase transcript cleavage. J. Biol. Chem. 2011; 286:18701. PubMed PMC

Borukhov S., Polyakov A., Nikiforov V., Goldfarb A.. GreA protein: a transcription elongation factor from Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 1992; 89:8899–8902. PubMed PMC

Fernández-Coll L., Potrykus K., Cashel M., Balsalobre C.. Mutational analysis of Escherichia coli GreA protein reveals new functional activity independent of antipause and lethal when overexpressed. Sci. Rep. 2020; 10:16074. PubMed PMC

Abdelkareem M., Saint-André C., Takacs M., Papai G., Crucifix C., Guo X., Ortiz J., Weixlbaumer A.. Structural basis of transcription: RNA polymerase backtracking and its reactivation. Mol. Cell. 2019; 75:298–309. PubMed PMC

Riaz-Bradley A., James K., Yuzenkova Y.. High intrinsic hydrolytic activity of cyanobacterial RNA polymerase compensates for the absence of transcription proofreading factors. Nucleic Acids Res. 2019; 48:1341–1352. PubMed PMC

Stevenson-Jones F., Woodgate J., Castro-Roa D., Zenkin N.. Ribosome reactivates transcription by physically pushing RNA polymerase out of transcription arrest. Proc. Natl. Acad. Sci. U.S.A. 2020; 117:8462–8467. PubMed PMC

Epshtein V., Nudler E.. Cooperation between RNA polymerase molecules in transcription elongation. Science. 2003; 300:801–805. PubMed

Epshtein V., Toulmé F., Rachid Rahmouni A., Borukhov S., Nudler E.. Transcription through the roadblocks: The role of RNA polymerase cooperation. EMBO J. 2003; 22:4719–4727. PubMed PMC

Šiková M., Wiedermannová J., Převorovský M., Barvík I., Sudzinová P., Kofroňová O., Benada O., Šanderová H., Condon C., Krásný L.. The torpedo effect in Bacillus subtilis: RN ase J1 resolves stalled transcription complexes. EMBO J. 2020; 39:e102500. PubMed PMC

Le T.T., Yang Y., Tan C., Suhanovsky M.M., Fulbright R.M., Inman J.T., Li M., Lee J., Perelman S., Roberts J.W.et al. .. Mfd dynamically regulates transcription via a release and catch-up mechanism. Cell. 2018; 172:344–357. PubMed PMC

Roberts J.W. Mechanisms of bacterial transcription termination. J. Mol. Biol. 2019; 431:4030–4039. PubMed

Kang J.Y., Llewellyn E., Chen J., Olinares P.D.B., Brewer J., Chait B.T., Campbell E.A., Darst S.A.. Structural basis for transcription complex 1 disruption by the mfd translocase. Elife. 2021; 10:e62117. PubMed PMC

Hawkins M., Dimude J.U., Howard J.A.L., Smith A.J., Dillingham M.S., Savery N.J., Rudolph C.J., Mcglynn P.. Direct removal of RNA polymerase barriers to replication by accessory replicative helicases. Nucleic Acids Res. 2019; 47:5100–5113. PubMed PMC

Wiedermannová J., Sudzinová P., Kovaľ T., Rabatinová A., Šanderová H., Ramaniuk O., Rittich Š., Dohnálek J., Fu Z., Halada P.et al. .. Characterization of HelD, an interacting partner of RNA polymerase from Bacillus subtilis. Nucleic Acids Res. 2014; 42:5151–5163. PubMed PMC

Sukhodolets M. V., Cabrera J.E., Zhi H., Jin Ding Jun. RapA, a bacterial homolog of SWI2/SNF2, stimulates RNA polymerase recycling in transcription. Genes Dev. 2001; 15:3330–3341. PubMed PMC

Porrua O., Boudvillain M., Libri D. Transcription termination: variations on common themes. Trends Genet. 2016; 32:508–522. PubMed

Ho H.N., van Oijen A.M., Ghodke H.. Single-molecule imaging reveals molecular coupling between transcription and DNA repair machinery in live cells. Nat. Commun. 2020; 11:1478. PubMed PMC

Windbichler N., Von Pelchrzim F., Mayer O., Csaszar E., Schroeder R.. Isolation of small RNA-binding proteins from E. coli: Evidence for frequent interaction of RNAs with RNA polymerase. RNA Biol. 2008; 5:30–40. PubMed

Walker J.E., Luyties O., Santangelo T.J.. Factor-dependent archaeal transcription termination. Proc. Natl. Acad. Sci. U.S.A. 2017; 114:E6767–E6773. PubMed PMC

Moreno-del Álamo M., Carrasco B., Torres R., Alonso J.C.. Bacillus subtilis PcrA helicase removes trafficking barriers. Cells. 2021; 10:935. PubMed PMC

Gwynn E.J., Smith A.J., Guy C.P., Savery N.J., McGlynn P., Dillingham M.S.. The conserved C-terminus of the PcrA/UvrD helicase interacts directly with RNA polymerase. PLoS One. 2013; 8:e78141. PubMed PMC

Epshtein V., Kamarthapu V., McGary K., Svetlov V., Ueberheide B., Proshkin S., Mironov A., Nudler E.. UvrD facilitates DNA repair by pulling RNA polymerase backwards. Nature. 2014; 505:372–377. PubMed PMC

Kouba T., Koval’ T., Sudzinová P., Pospíšil J., Brezovská B., Hnilicová J., Šanderová H., Janoušková M., Šiková M., Halada P.et al. .. Mycobacterial HelD is a nucleic acids-clearing factor for RNA polymerase. Nat. Commun. 2020; 11:6419. PubMed PMC

Newing T.P., Oakley A.J., Miller M., Dawson C.J., Brown S.H.J., Bouwer J.C., Tolun G., Lewis P.J.. Molecular basis for RNA polymerase-dependent transcription complex recycling by the helicase-like motor protein HelD. Nat. Commun. 2020; 11:6420. PubMed PMC

Pei H.H., Hilal T., Chen Z.A., Huang Y.H., Gao Y., Said N., Loll B., Rappsilber J., Belogurov G.A., Artsimovitch I.et al. .. The δ subunit and NTPase HelD institute a two-pronged mechanism for RNA polymerase recycling. Nat. Commun. 2020; 11:6418. PubMed PMC

Sukhodolets M. V., Jin D.J.. RapA, a novel RNA polymerase-associated protein, is a bacterial homolog of SWI2*SNF2. J. Biol. Chem. 1998; 273:7018–7023. PubMed

Liu B., Zuo Y., Steitz T.A., Yang W.. Structural basis for transcription reactivation by RapA. Proc. Natl. Acad. Sci. U.S.A. 2015; 112:2006–2010. PubMed PMC

Tufegdzic Vidakovic A., Harreman M., Dirac-Svejstrup A.B., Boeing S., Roy A., Encheva V., Neumann M., Wilson M., Snijders A.P., Svejstrup J.Q. Analysis of RNA polymerase II ubiquitylation and proteasomal degradation. Methods. 2019; 159–160:146–156. PubMed PMC

Wilson M.D., Harreman M., Svejstrup J.Q.. Ubiquitylation and degradation of elongating RNA polymerase II: The last resort. Biochim. Biophys. Acta - Gene Regul. Mech. 2013; 1829:151–157. PubMed

Lommel L., Bucheli M.E., Sweder K.S.. Transcription-coupled repair in yeast is independent from ubiquitylation of RNA pol II: implications for Cockayne's syndrome. Proc. Natl. Acad. Sci. 2000; 97:9088–9092. PubMed PMC

Somesh B.P., Reid J., Liu W.F., Søgaard T.M.M., Erdjument-Bromage H., Tempst P., Svejstrup J.Q.. Multiple mechanisms confining RNA polymerase II ubiquitylation to polymerases undergoing transcriptional arrest. Cell. 2005; 121:913–923. PubMed

Somesh B.P., Sigurdsson S., Saeki H., Erdjument-Bromage H., Tempst P., Svejstrup J.Q.. Communication between distant sites in RNA polymerase II through ubiquitylation factors and the polymerase CTD. Cell. 2007; 129:57–68. PubMed

Nouspikel T. Multiple roles of ubiquitination in the control of nucleotide excision repair. Mech. Ageing Dev. 2011; 132:355–365. PubMed

Nakazawa Y., Hara Y., Oka Y., Yamanaka K., Luijsterburg M.S., Correspondence T.O.. Ubiquitination of DNA damage-stalled RNAPII promotes transcription-coupled repair. Cell. 2020; 180:1228–1244. PubMed

Colin J., Candelli T., Porrua O., Boulay J., Zhu C., Lacroute F., Steinmetz L.M., Libri D. Roadblock termination by reb1p restricts cryptic and readthrough transcription. Mol. Cell. 2014; 56:667–680. PubMed

Candelli T., Challal D., Briand J., Boulay J., Porrua O., Colin J., Libri D. High-resolution transcription maps reveal the widespread impact of roadblock termination in yeast. EMBO J. 2018; 37:e97490. PubMed PMC

Peters J.M., Vangeloff A.D., Landick R.. Bacterial transcription terminators: The RNA 3′-end chronicles. J. Mol. Biol. 2011; 412:793–813. PubMed PMC

Zhu A.Q., Von Hippel P.H. Rho-dependent termination within the trp t’ terminator. I. Effects of Rho loading and template sequence. Biochemistry. 1998; 37:11202–11214. PubMed

Peters J.M., Mooney R.A., Kuan P.F., Rowland J.L., Keleş S., Landick R.. Rho directs widespread termination of intragenic and stable RNA transcription. Proc. Natl. Acad. Sci. U.S.A. 2009; 106:15406–15411. PubMed PMC

Mitra P., Ghosh G., Hafeezunnisa M., Sen R.. Rho protein: roles and mechanisms. Annu. Rev. Microbiol. 2017; 71:687–709. PubMed

Hao Z., Epshtein V., Kim K.H., Proshkin S., Svetlov V., Kamarthapu V., Bharati B., Mironov A., Walz T., Nudler E.. Pre-termination transcription complex: structure and function. Mol. Cell. 2021; 81:281–292. PubMed PMC

Peters J.M., Mooney R.A., Grass J.A., Jessen E.D., Tran F., Landick R.. Rho and NusG suppress pervasive antisense transcription in Escherichia coli. Genes Dev. 2012; 26:2621–2633. PubMed PMC

Kotlajich M. V., Hron D.R., Boudreau B.A., Sun Z., Lyubchenko Y.L., Landick R.. Bridged filaments of histone-like nucleoid structuring protein pause RNA polymerase and aid termination in bacteria. Elife. 2015; 2015:e04970. PubMed PMC

Said N., Hilal T., Sunday N.D., Khatri A., Bürger J., Mielke T., Belogurov G.A., Loll B., Sen R., Artsimovitch I.et al. .. Steps toward translocation-independent RNA polymerase inactivation by terminator ATPase p. Science. 2021; 371:6524. PubMed PMC

Nicolas P., Mäder U., Dervyn E., Rochat T., Leduc A., Pigeonneau N., Bidnenko E., Marchadier E., Hoebeke M., Aymerich S.et al. .. Condition-dependent transcriptome reveals high-level regulatory architecture in Bacillus subtilis. Science. 2012; 335:1103–1106. PubMed

Ray-Soni A., Bellecourt M.J., Landick R.. Mechanisms of bacterial transcription termination: all good things must end. Annu. Rev. Biochem. 2016; 85:319–347. PubMed

Nielsen S., Yuzenkova Y., Zenkin N.. Mechanism of eukaryotic RNA polymerase III transcription termination. Science. 2013; 340:1577–1580. PubMed PMC

Zenkin N. Ancient RNA stems that terminate transcription. RNA Biol. 2014; 11:295–297. PubMed PMC

Rivosecchi J., Larochelle M., Teste C., Grenier F., Malapert A., Ricci E.P., Bernard P., Bachand F., Vanoosthuyse V.. Senataxin homologue Sen1 is required for efficient termination of RNA polymerase III transcription. EMBO J. 2019; 38:e101955. PubMed PMC

Eaton J.D., Davidson L., Bauer D.L.V., Natsume T., Kanemaki M.T., West S.. Xrn2 accelerates termination by RNA polymerase II, which is underpinned by CPSF73 activity. Genes Dev. 2018; 32:127–139. PubMed PMC

Kim M., Krogan N.J., Vasiljeva L., Rando O.J., Nedea E., Greenblatt J.F., Buratowski S.. The yeast Rat1 exonuclease promotes transcription termination by RNA polymerase II. Nature. 2004; 432:517–522. PubMed

Teixeira A., Tahiri-Alaoui A., West S., Thomas B., Ramadass A., Martianov I., Dye M., James W., Proudfoot N.J., Akoulitchev A.. Autocatalytic RNA cleavage in the human β-globin pre-mRNA promotes transcription termination. Nature. 2004; 432:526–530. PubMed

West S., Gromak N., Proudfoot N.J.. Human 5′ → 3′ exonuclease Xrn2 promotes transcription termination at co-transcriptional cleavage sites. Nature. 2004; 432:522–525. PubMed

Cortazar M.A., Sheridan R.M., Erickson B., Fong N., Glover-Cutter K., Brannan K., Bentley D.L.. Control of RNA Pol II speed by PNUTS-PP1 and Spt5 dephosphorylation facilitates termination by a “Sitting Duck Torpedo” mechanism. Mol. Cell. 2019; 76:896–908. PubMed PMC

Kecman T., Kuś K., Heo D.H., Duckett K., Birot A., Liberatori S., Mohammed S., Geis-Asteggiante L., Robinson C. V., Vasiljeva L.. Elongation/termination factor exchange mediated by PP1 phosphatase orchestrates transcription termination. Cell Rep. 2018; 25:259–269. PubMed PMC

Eaton J.D., Francis L., Davidson L., West S.. A unified allosteric/torpedo mechanism for transcriptional termination on human protein-coding genes. Genes Dev. 2020; 34:132–145. PubMed PMC

Rondon A.G., Mischo H.E., Proudfoot N.J.. Terminating transcription in yeast: whether to be a ‘nerd’ or a ‘rat. Nat. Struct. Mol. Biol. 2008; 15:775–776. PubMed

Yang X.-C., Sullivan K.D., Marzluff W.F., Dominski Z.. Studies of the 5′ exonuclease and endonuclease activities of CPSF-73 in histone Pre-mRNA processing. Mol. Cell. Biol. 2009; 29:31–42. PubMed PMC

Yang X., Sun Y., Aik W.S., Marzluff W.F., Tong L., Dominski Z.. Studies with recombinant U7 snRNP demonstrate that CPSF73 is both an endonuclease and a 5′–3′ exonuclease. RNA. 2020; 26:1345–1359. PubMed PMC

Baillat D., Hakimi M.A., Näär A.M., Shilatifard A., Cooch N., Shiekhattar R.. Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II. Cell. 2005; 123:265–276. PubMed

Fong N., Brannan K., Erickson B., Kim H., Cortazar M.A., Sheridan R.M., Nguyen T., Karp S., Bentley D.L.. Effects of transcription elongation rate and Xrn2 exonuclease activity on RNA polymerase II termination suggest widespread kinetic competition. Mol. Cell. 2015; 60:256–267. PubMed PMC

Dominski Z., Yang X.C., Marzluff W.F.. The polyadenylation factor CPSF-73 is involved in histone-pre-mRNA processing. Cell. 2005; 123:37–48. PubMed

Chodchoy N., Pandey N.B., Marzluff W.F.. An intact histone 3’-processing site is required for transcription termination in a mouse histone H2a gene. Mol. Cell. Biol. 1991; 11:497–509. PubMed PMC

Tatomer D.C., Elrod N.D., Liang D., Xiao M.S., Jiang J.Z., Jonathan M., Huang K.L., Wagner E.J., Cherry S., Wilusz J.E.. The Integrator complex cleaves nascent mRNAs to attenuate transcription. Genes Dev. 2019; 33:1525–1538. PubMed PMC

Skaar J.R., Ferris A.L., Wu X., Saraf A., Khanna K.K., Florens L., Washburn M.P., Hughes S.H., Pagano M.. The Integrator complex controls the termination of transcription at diverse classes of gene targets. Cell Res. 2015; 25:288–305. PubMed PMC

Gómez-Orte E., Sáenz-Narciso B., Zheleva A., Ezcurra B., de Toro M., López R., Gastaca I., Nilsen H., Sacristán M.P., Schnabel R.et al. .. Disruption of the Caenorhabditis elegans Integrator complex triggers a non-conventional transcriptional mechanism beyond snRNA genes. PLoS Genet. 2019; 15:e1007981. PubMed PMC

Maier L.K., Marchfelder A.. It's all about the T: transcription termination in Archaea. Biochem. Soc. Trans. 2019; 47:461–468. PubMed

Sanders T.J., Wenck B.R., Selan J.N., Barker M.P., Trimmer S.A., Walker J.E., Santangelo T.J.. FttA is a CPSF73 homologue that terminates transcription in Archaea. Nat. Microbiol. 2020; 5:545–553. PubMed PMC

Yue L., Li J., Zhang B., Qi L., Li Z., Zhao F., Li L., Zheng X., Dong X.. The conserved ribonuclease aCPSF1 triggers genome-wide transcription termination of Archaea via a 3’-end cleavage mode. Nucleic Acids Res. 2020; 48:9589–9605. PubMed PMC

Wagschal A., Rousset E., Basavarajaiah P., Contreras X., Harwig A., Laurent-Chabalier S., Nakamura M., Chen X., Zhang K., Meziane O.et al. .. Microprocessor, Setx, Xrn2, and Rrp6 co-operate to induce premature termination of transcription by RNAPII. Cell. 2012; 150:1147–1157. PubMed PMC

Brannan K., Kim H., Erickson B., Glover-Cutter K., Kim S., Fong N., Kiemele L., Hansen K., Davis R., Lykke-Andersen J.et al. .. MRNA decapping factors and the exonuclease Xrn2 function in widespread premature termination of RNA polymerase II transcription. Mol. Cell. 2012; 46:311–324. PubMed PMC

Hara R., Selby C.P., Liu M., Price D.H., Sancar A.. Human transcription release factor 2 dissociates RNA polymerases I and II stalled at a cyclobutane thymine dimer. J. Biol. Chem. 1999; 274:24779–24786. PubMed

Liu M., Xie Z., Price D.H.. A human RNA polymerase II transcription termination factor is a SWI2/SNF2 family member. J. Biol. Chem. 1998; 273:25541–25544. PubMed

Lai F., Damle S.S., Ling K.K., Rigo F.. Directed RNase H cleavage of nascent transcripts causes transcription termination. Mol. Cell. 2020; 77:1032–1043. PubMed

Lee J.S., Mendell J.T.. Antisense-mediated transcript knockdown triggers premature transcription termination. Mol. Cell. 2020; 77:1044–1054. PubMed PMC

Haimovich G., Medina D.A., Causse S.Z., Garber M., Millán-Zambrano G., Barkai O., Chávez S., Pérez-Ortín J.E., Darzacq X., Choder M.. Gene expression is circular: Factors for mRNA degradation also foster mRNA synthesis. Cell. 2013; 153:1000. PubMed

Luo W., Johnson A.W., Bentley D.L.. The role of Rat1 in coupling mRNA 3′-end processing to transcription termination: Implications for a unified allosteric-torpedo model. Genes Dev. 2006; 20:954–965. PubMed PMC

Luciano D.J., Vasilyev N., Richards J., Serganov A., Belasco J.G.. A novel RNA phosphorylation state enables 5′ end-dependent degradation in Escherichia coli. Mol. Cell. 2017; 67:44–54. PubMed PMC

Richards J., Liu Q., Pellegrini O., Celesnik H., Yao S., Bechhofer D.H., Condon C., Belasco J.G.. An RNA pyrophosphohydrolase triggers 5′-exonucleolytic degradation of mRNA in Bacillus subtilis. Mol. Cell. 2011; 43:940–949. PubMed PMC

Frindert J., Zhang Y., Nübel G., Kahloon M., Kolmar L., Hotz-Wagenblatt A., Burhenne J., Haefeli W.E., Jäschke A.. Identification, biosynthesis, and decapping of NAD-capped RNAs in B. subtilis. Cell Rep. 2018; 24:1890–1901. PubMed

Jones C.I., Zabolotskaya M.V., Newbury S.F.. The 5′ → 3′ exoribonuclease XRN1/Pacman and its functions in cellular processes and development. Wiley Interdiscip. Rev. RNA. 2012; 3:455–468. PubMed

Hudeček O., Benoni R., Reyes-Gutierrez P.E., Culka M., Šanderová H., Hubálek M., Rulíšek L., Cvačka J., Krásný L., Cahová H.. Dinucleoside polyphosphates act as 5′-RNA caps in bacteria. Nat. Commun. 2020; 11:1052. PubMed PMC

Wang J., Alvin Chew B.L., Lai Y., Dong H., Xu L., Balamkundu S., Cai W.M., Cui L., Liu C.F., Fu X.-Y.et al. .. Quantifying the RNA cap epitranscriptome reveals novel caps in cellular and viral RNA. Nucleic Acids Res. 2019; 47:e130. PubMed PMC

Bird J.G., Zhang Y., Tian Y., Panova N., Barvík I., Greene L., Liu M., Buckley B., Krásný L., Lee J.K.et al. .. The mechanism of RNA 5′ capping with NAD+, NADH and desphospho-CoA. Nature. 2016; 535:444–447. PubMed PMC

Julius C., Yuzenkova Y.. Bacterial RNA polymerase caps RNA with various cofactors and cell wall precursors. Nucleic Acids Res. 2017; 45:8282–8290. PubMed PMC

Sharma S., Grudzien-Nogalska E., Hamilton K., Jiao X., Yang J., Tong L., Kiledjian M.. Mammalian Nudix proteins cleave nucleotide metabolite caps on RNAs. Nucleic Acids Res. 2020; 48:6788–6798. PubMed PMC

Song M.G., Bail S., Kiledjian M.. Multiple Nudix family proteins possess mRNA decapping activity. RNA. 2013; 19:390–399. PubMed PMC

Mathy N., Bénard L., Pellegrini O., Daou R., Wen T., Condon C.. 5′-to-3′ Exoribonuclease activity in bacteria: role of RNase J1 in rRNA maturation and 5′ stability of mRNA. Cell. 2007; 129:681–692. PubMed

Nagarajan V.K., Jones C.I., Newbury S.F., Green P.J.. XRN 5′→3′ exoribonucleases: structure, mechanisms and functions. Biochim. Biophys. Acta - Gene Regul. Mech. 2013; 1829:590–603. PubMed PMC

Mathy N., Hébert A., Mervelet P., Bénard L., Dorléans A., Li De La, Sierra-Gallay I., Noirot P., Putzer H., Condon C.. Bacillus subtilis ribonucleases J1 and J2 form a complex with altered enzyme behaviour. Mol. Microbiol. 2010; 75:489–498. PubMed

Dominski Z., Carpousis A.J., Clouet-d’Orval B.. Emergence of the β-CASP ribonucleases: highly conserved and ubiquitous metallo-enzymes involved in messenger RNA maturation and degradation. Biochim. Biophys. Acta - Gene Regul. Mech. 2013; 1829:532–551. PubMed

Wu Y., Albrecht T.R., Baillat D., Wagner E.J., Tong L.. Molecular basis for the interaction between Integrator subunits IntS9 and IntS11 and its functional importance. Proc. Natl. Acad. Sci. U.S.A. 2017; 114:4394–4399. PubMed PMC

Callebaut I., Moshous D., Mornon J.P., De Villartay J.P.. Metallo-β-lactamase fold within nucleic acids processing enzymes: The β-CASP family. Nucleic Acids Res. 2002; 30:3592–3601. PubMed PMC

Skrajna A., Yang X.C., Bucholc K., Zhang J., Hall T.M.T., Dadlez M., Marzluff W.F., Dominski Z.. U7 snRNP is recruited to histone pre-mRNA in a FLASH-dependent manner by two separate regions of the stem-loop binding protein. RNA. 2017; 23:938–951. PubMed PMC

Marz M., Mosig A., Stadler B.M.R., Stadler P.F.. U7 snRNAs: A Computational Survey. Genomic, Proteomics Bioinforma. 2007; 5:187–195. PubMed PMC

Pedersen K., Zavialov A. V., Pavlov M.Y., Elf J., Gerdes K., Ehrenberg M.. The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site. Cell. 2003; 112:131–140. PubMed

Vesper O., Amitai S., Belitsky M., Byrgazov K., Kaberdina A.C., Engelberg-Kulka H., Moll I.. Selective translation of leaderless mRNAs by specialized ribosomes generated by MazF in Escherichia coli. Cell. 2011; 147:147–157. PubMed PMC

Mets T., Kasvandik S., Saarma M., Maiväli Ü., Tenson T., Kaldalu N.. Fragmentation of Escherichia coli mRNA by MazF and MqsR. Biochimie. 2019; 156:79–91. PubMed

Demo G., Rasouly A., Vasilyev N., Svetlov V., Loveland A.B., Diaz-Avalos R., Grigorieff N., Nudler E., Korostelev A.A.. Structure of RNA polymerase bound to ribosomal 30S subunit. Elife. 2017; 6:e28560. PubMed PMC

Johnson G.E., Lalanne J.-B., Peters M.L., Li G.-W.. Functionally uncoupled transcription–translation in Bacillus subtilis. Nat. 2020; 585:124–128. PubMed PMC

Callen B.P., Shearwin K.E., Egan J.B.. Transcriptional interference between convergent promoters caused by elongation over the promoter. Mol. Cell. 2004; 14:647–656. PubMed

Artsimovitch I., Landick R.. Pausing by bacterial RNA polymerase is mediated by mechanistically distinct classes of signals. Proc. Natl. Acad. Sci. U.S.A. 2000; 97:7090–7095. PubMed PMC

Skourti-Stathaki K., Proudfoot N.J., Gromak N.. Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination. Mol. Cell. 2011; 42:794–805. PubMed PMC

Crossley M.P., Bocek M., Cimprich K.A.. R-Loops as cellular regulators and genomic threats. Mol. Cell. 2019; 73:398–411. PubMed PMC

Schwalb B., Michel M., Zacher B., Hauf K.F., Demel C., Tresch A., Gagneur J., Cramer P.. TT-seq maps the human transient transcriptome. Science. 2016; 352:1225–1228. PubMed

Kerppola T.K., Kane C.M.. Analysis of the signals for transcription termination by purified RNA polymerase II. Biochemistry. 1990; 29:269–278. PubMed

Bochkareva A., Yuzenkova Y., Tadigotla V.R., Zenkin N.. Factor-independent transcription pausing caused by recognition of the RNA-DNA hybrid sequence. EMBO J. 2012; 31:630–639. PubMed PMC

Újvári A., Pal M., Luse D.S.. RNA polymerase II transcription complexes may become arrested if the nascent RNA is shortened to less than 50 nucleotides. J. Biol. Chem. 2002; 277:32527–32537. PubMed

Kusuya Y., Kurokawa K., Ishikawa S., Ogasawara N., Oshima T.. Transcription factor GreA contributes to resolving promoter-proximal pausing of RNA polymerase in Bacillus subtilis cells. J. Bacteriol. 2011; 193:3090–3099. PubMed PMC

Xiang S., Cooper-Morgan A., Jiao X., Kiledjian M., Manley J.L., Tong L.. Structure and function of the 5′→3′ exoribonuclease Rat1 and its activating partner Rai1. Nat. 2009; 458:784–788. PubMed PMC

Park J., Kang M., Kim M.. Unraveling the mechanistic features of RNA polymerase II termination by the 5′–3′ exoribonuclease Rat1. Nucleic Acids Res. 2015; 43:2625–2637. PubMed PMC

Dorléans A., Li De La, Sierra-Gallay I., Piton J., Zig L., Gilet L., Putzer H., Condon C.. Molecular basis for the recognition and cleavage of RNA by the bifunctional 5′–3′ exo/endoribonuclease RNase J. Structure. 2011; 19:1252–1261. PubMed

Tollervey D. Termination by torpedo. Nature. 2004; 432:456–457. PubMed

Miki T.S., Carl S.H., Großhans H.. Two distinct transcription termination modes dictated by promoters. Genes Dev. 2017; 31:1870–1879. PubMed PMC

Pearson E.L., Moore C.L.. Dismantling promoter-driven RNA polymerase ii transcription complexes in vitro by the termination factor Rat1. J. Biol. Chem. 2013; 288:19750–19759. PubMed PMC

Lang W.H., Platt T., Reeder R.H.. Escherichia coli rho factor induces release of yeast RNA polymerase II but not polymerase I or III. Proc. Natl. Acad. Sci. U.S.A. 1998; 95:4900–4905. PubMed PMC

Epshtein V., Cardinale C.J., Ruckenstein A.E., Borukhov S., Nudler E.. An allosteric path to transcription termination. Mol. Cell. 2007; 28:991–1001. PubMed

Epshtein V., Dutta D., Wade J., Nudler E.. An allosteric mechanism of Rho-dependent transcription termination. Nature. 2010; 463:245–249. PubMed PMC

Gimpel M., Brantl S.. Dual-function sRNA encoded peptide SR1P modulates moonlighting activity of B. subtilis GapA. RNA Biol. 2016; 13:916–926. PubMed PMC

Sharwood R.E., Halpert M., Luro S., Schuster G., Stern D.B.. Chloroplast RNase J compensates for inefficient transcription termination by removal of antisense RNA. RNA. 2011; 17:2165–2176. PubMed PMC

Legen J., Kemp S., Krause K., Profanter B., Herrmann R.G., Maier R.M.. Comparative analysis of plastid transcription profiles of entire plastid chromosomes from tobacco attributed to wild-type and PEP-deficient transcription machineries. Plant J. 2002; 31:171–188. PubMed

Ji D., Manavski N., Meurer J., Zhang L., Chi W.. Regulated chloroplast transcription termination. Biochim. Biophys. Acta - Bioenerg. 2019; 1860:69–77. PubMed

Halpert M., Liveanu V., Glaser F., Schuster G.. The Arabidopsis chloroplast RNase J displays both exo- and robust endonucleolytic activities. Plant Mol. Biol. 2019; 99:17–29. PubMed

Condon C., Gilet L.. Nicholson A. The metallo-β-lactamase family of ribonucleases. Ribonucleases. Nucleic Acids and Molecular Biology. 2011; Berlin, Heidelberg: Springer; 245–267.

Liponska A., Jamalli A., Kuras R., Suay L., Garbe E., Wollman F.A., Laalami S., Putzer H.. Tracking the elusive 5′ exonuclease activity of Chlamydomonas reinhardtii RNase J. Plant Mol. Biol. 2018; 96:641–653. PubMed

Nishida Y., Ishikawa H., Baba S., Nakagawa N., Kuramitsu S., Masui R.. Crystal structure of an archaeal cleavage and polyadenylation specificity factor subunit from Pyrococcus horikoshii. Proteins Struct. Funct. Bioinforma. 2010; 78:2395–2398. PubMed

Mir-Montazeri B., Ammelburg M., Forouzan D., Lupas A.N., Hartmann M.D.. Crystal structure of a dimeric archaeal cleavage and polyadenylation specificity factor. J. Struct. Biol. 2011; 173:191–195. PubMed

Zheng X., Feng N., Li D., Dong X., Li J. New molecular insights into an archaeal RNase J reveal a conserved processive exoribonucleolysis mechanism of the RNase J family. Mol. Microbiol. 2017; 106:351–366. PubMed

Jinek M., Coyle S.M., Doudna J.A.. Coupled 5′ nucleotide recognition and processivity in Xrn1-mediated mRNA decay. Mol. Cell. 2011; 41:600–608. PubMed PMC

Svetlov V., Nudler E.. Towards the unified principles of transcription termination. EMBO J. 2020; 39:e104112. PubMed PMC

Ghodge S. V., Raushel F.M.. Discovery of a previously unrecognized ribonuclease from Escherichia coli that hydrolyzes 5′-phosphorylated fragments of RNA. Biochemistry. 2015; 54:2911–2918. PubMed

Jain C. RNase AM, a 5′ to 3′ exonuclease, matures the 5′ end of all three ribosomal RNAs in E. coli. Nucleic Acids Res. 2020; 48:5616–5623. PubMed PMC

Britton R.A., Wen T., Schaefer L., Pellegrini O., Uicker W.C., Mathy N., Tobin C., Daou R., Szyk J., Condon C.. Maturation of the 5′ end of Bacillus subtilis 16S rRNA by the essential ribonuclease YkqC/RNase J1. Mol. Microbiol. 2007; 63:127–138. PubMed

DiChiara J.M., Liu B., Figaro S., Condon C., Bechhofer D.H.. Mapping of internal monophosphate 5′ ends of Bacillus subtilis messenger RNAs and ribosomal RNAs in wild-type and ribonuclease-mutant strains. Nucleic Acids Res. 2016; 44:3373–3389. PubMed PMC

Redko Y., Condon C.. Maturation of 23S rRNA in Bacillus subtilis in the absence of mini-III. J. Bacteriol. 2010; 192:356–359. PubMed PMC

Henras A.K., Plisson-Chastang C., O′Donohue M.-F., Chakraborty A., Gleizes P.-E.. An overview of pre-ribosomal RNA processing in eukaryotes. Wiley Interdiscip. Rev. RNA. 2015; 6:225. PubMed PMC

Dominski Z. Nucleases of the metallo-β-lactamase family and their role in DNA and RNA metabolism. Crit. Rev. Biochem. Mol. Biol. 2007; 42:67–93. PubMed

Marzluff W.F., Koreski K.P.. Birth and death of histone mRNAs. Trends Genet. 2017; 33:745–759. PubMed PMC

Sun Y., Zhang Y., Aik W.S., Yang X.C., Marzluff W.F., Walz T., Dominski Z., Tong L.. Structure of an active human histone pre-mRNA 3′-end processing machinery. Science. 2020; 367:700–703. PubMed PMC

Baejen C., Andreani J., Torkler P., Battaglia S., Schwalb B., Lidschreiber M., Maier K.C., Boltendahl A., Rus P., Esslinger S.et al. .. Genome-wide analysis of RNA polymerase II termination at protein-coding genes. Mol. Cell. 2017; 66:38–49. PubMed

Johnson A.W. Rat1p and Xrn1p are functionally interchangeable exoribonucleases that are restricted to and required in the nucleus and cytoplasm, respectively. Mol. Cell. Biol. 1997; 17:6122–6130. PubMed PMC

Roberts J.W. Termination factor for RNA synthesis. Nature. 1969; 224:1168–1174. PubMed

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