Continuous and Discontinuous RNA Synthesis in Coronaviruses
Open accessAbstract
Replication of the coronavirus genome requires continuous RNA synthesis, whereas transcription is a discontinuous process unique among RNA viruses. Transcription includes a template switch during the synthesis of subgenomic negative-strand RNAs to add a copy of the leader sequence. Coronavirus transcription is regulated by multiple factors, including the extent of base-pairing between transcription-regulating sequences of positive and negative polarity, viral and cell protein–RNA binding, and high-order RNA-RNA interactions. Coronavirus RNA synthesis is performed by a replication-transcription complex that includes viral and cell proteins that recognize cis-acting RNA elements mainly located in the highly structured 5′ and 3′ untranslated regions. In addition to many viral nonstructural proteins, the presence of cell nuclear proteins and the viral nucleocapsid protein increases virus amplification efficacy. Coronavirus RNA synthesis is connected with the formation of double-membrane vesicles and convoluted membranes. Coronaviruses encode proofreading machinery, unique in the RNA virus world, to ensure the maintenance of their large genome size.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Coronaviruses generate subgenomic mRNAs for translating structural proteins including the spike protein.
“Coronaviruses generate subgenomic mRNAs for translating structural proteins including the spike protein [59,60].”
From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [59]
The CORONAVIRUS REPLICATION AND TRANSCRIPTION section states that coronavirus transcription produces subgenomic mRNAs encoding structural proteins, and the REGULATION OF CORONAVIRUS PROTEIN STOICHIOMETRIC RATIOS section describes their translation into viral proteins. The passages do not identify spike specifically as one of those proteins, so that detail is not verified by our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The GAIT system: a gatekeeper of inflammatory gene expression
Mukhopadhyay, R., Jia, J., Arif, A., Ray, P. S., & Fox, P. L. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.03.004 · Cited by 216 · see citing works
Flagged first, then by citations
Research works printed but not linked: 163
- [1]de Groot RJ Baker SC Baric R Enjuanes L Gorbalenya AE 2012 Coronaviridae Virus Taxonomy: Ninth Report of the International Committee on Taxonomy of Viruses King AMQ Adams MJ Carstens EB Lefkowitz EJ 774 96 San Diego, CA Elsevier Academic
- [2]Coleman CM Frieman MB 2014 Coronaviruses: important emerging human pathogens J Virol 88 5209 12 24600003 PMC4019136
- [3]Marthaler D Raymond L Jiang Y Collins J Rossow K Rovira A 2014 Rapid detection, complete genome sequencing, and phylogenetic analysis of porcine deltacoronavirus Emerg Infect Dis 20 1347 50 25075556 PMC4111195
- [4]Huang YW Dickerman AW Pineyro P Li L Fang L 2013 Origin, evolution, and genotyping of emergent porcine epidemic diarrhea virus strains in the United States mBio 4 e00737 13 24129257 PMC3812708
- [5]Masters PS 2006 The molecular biology of coronaviruses Adv Virus Res 66 193 292 16877062 PMC7112330
- [6]Firth AE Brierley I 2012 Non-canonical translation in RNA viruses J Gen Virol 93 1385 409 22535777 PMC3542737
- [7]Enjuanes L Almazan F Sola I Zuñiga S 2006 Biochemical aspects of coronavirus replication and virus-host interaction Annu Rev Microbiol 60 211 30 16712436
- [8]Lai MMC Cavanagh D 1997 The molecular biology of coronaviruses Adv Virus Res 48 1 100 9233431 PMC7130985
- [9]Sola I Mateos-Gomez PA Almazan F Zuñiga S Enjuanes L 2011 RNA-RNA and RNA-protein interactions in coronavirus replication and transcription RNA Biol 8 237 48 21378501 PMC3230552
- [10]Enjuanes L Gorbalenya AE de Groot RJ Cowley JA Ziebuhr J Snijder EJ 2008 The Nidovirales Encyclopedia of Virology Mahy BWJ Van Regenmortel M Walker P Majumder-Russell D 419 30 Oxford, UK Elsevier 3rd
- [11]Sawicki SG Sawicki DL 1998 A new model for coronavirus transcription Adv Exp Med Biol 440 215 19 9782283
- [13]Miller WA Koev G 2000 Synthesis of subgenomic RNAs by positive-strand RNA virus Virology 273 1 8 10891401
- [14]Pasternak AO Spaan WJ Snijder EJ 2006 Nidovirus transcription: how to make sense? J Gen Virol 87 1403 21 16690906
- [15]Huang C Lokugamage KG Rozovics JM Narayanan K Semler BL Makino S 2011 SARS coronavirus nsp1 protein induces template-dependent endonucleolytic cleavage of mRNAs: viral mRNAs are resistant to nsp1-induced RNA cleavage PLOS Pathog 7 e1002433 22174690 PMC3234236
- [16]Alonso S Izeta A Sola I Enjuanes L 2002 Transcription regulatory sequences and mRNA expression levels in the coronavirus transmissible gastroenteritis virus J Virol 76 1293 308 11773405 PMC135778
- [17]Zuñiga S Sola I Alonso S Enjuanes L 2004 Sequence motifs involved in the regulation of discontinuous coronavirus subgenomic RNA synthesis J Virol 78 980 94 Proposes a working model of coronavirus transcription based on the role of transcription-regulating sequence complementarity. 14694129 PMC368802
- [18]Pasternak AO van den Born E Spaan WJ Snijder EJ 2001 Sequence requirements for RNA strand transfer during nidovirus discontinuous subgenomic RNA synthesis EMBO J 20 7220 28 Describes the role of transcription-regulating sequence complementarity in arterivirus transcription. 11742998 PMC125340
- [19]van Marle G Dobbe JC Gultyaev AP Luytjes W Spaan WJM Snijder EJ 1999 Arterivirus discontinuous mRNA transcription is guided by base pairing between sense and antisense transcription-regulating sequences PNAS 96 12056 61 10518575 PMC18411
- [20]Pasternak AO van den Born E Spaan WJM Snijder EJ 2003 The stability of the duplex between sense and antisense transcription-regulating sequences is a crucial factor in arterivirus subgenomic mRNA synthesis J Virol 77 1175 83 12502834 PMC140805
- [21]Sola I Moreno JL Zuñiga S Alonso S Enjuanes L 2005 Role of nucleotides immediately flanking the transcription-regulating sequence core in coronavirus subgenomic mRNA synthesis J Virol 79 2506 16 Reports the relevance of sequence complementarity and transcription-regulating sequence composition in coronavirus transcription. 15681451 PMC546574
- [22]Nagy PD Simon AE 1997 New insights into the mechanisms of RNA recombination Virology 235 1 9 9300032
- [23]Dufour D Mateos-Gomez PA Enjuanes L Gallego J Sola I 2011 Structure and functional relevance of a transcription-regulating sequence involved in coronavirus discontinuous RNA synthesis J Virol 85 4963 73 21389138 PMC3126183
- [24]Chang RY Krishnan R Brian DA 1996 The UCUAAAC promoter motif is not required for high-frequency leader recombination in bovine coronavirus defective interfering RNA J Virol 70 2720 29 8627745 PMC190128
- [25]Moreno JL Zuñiga S Enjuanes L Sola I 2008 Identification of a coronavirus transcription enhancer J Virol 82 3882 93 18272586 PMC2292980
- [26]Mateos-Gomez PA Zuñiga S Palacio L Enjuanes L Sola I 2011 Gene N proximal and distal RNA motifs regulate coronavirus nucleocapsid mRNA transcription J Virol 85 8968 80 21715479 PMC3165819
- [27]Mateos-Gomez PA Morales L Zuñiga S Enjuanes L Sola I 2013 Long-distance RNA-RNA interactions in the coronavirus genome form high-order structures promoting discontinuous RNA synthesis during transcription J Virol 87 177 86 Describes the longest RNA-RNA interaction known so far, leading to a high-order structure controlling coronavirus transcription. 23055566 PMC3536410
- [28]Nicholson BL White KA 2014 Functional long-range RNA-RNA interactions in positive-strand RNA viruses Nat Rev Microbiol 12 493 504 24931042 PMC7097572
- [29]Sawicki SG Sawicki DL Siddell SG 2007 A contemporary view of coronavirus transcription J Virol 81 20 29 16928755 PMC1797243
- [30]Almazan F Galán C Enjuanes L 2004 The nucleoprotein is required for efficient coronavirus genome replication J Virol 78 12683 88 15507657 PMC525053
- [31]Zuñiga S Cruz JL Sola I Mateos-Gomez PA Palacio L Enjuanes L 2010 Coronavirus nucle-ocapsid protein facilitates template switching and is required for efficient transcription J Virol 84 2169 75 Reports the relevance of the N protein in coronavirus transcription and template switching. 19955314 PMC2812394
- [32]Brockway SM Lu XT Peters TR Dermody TS Denison MR 2004 Intracellular localization and protein interactions of the gene 1 protein p28 during mouse hepatitis virus replication J Virol 78 11551 62 15479796 PMC523235
- [33]Nedialkova DD Gorbalenya AE Snijder EJ 2010 Arterivirus nsp1 modulates the accumulation of minus-strand templates to control the relative abundance of viral mRNAs PLOS Pathog 6 e1000772 20174607 PMC2824749
- [34]Wu CH Chen PJ Yeh SH 2014 Nucleocapsid phosphorylation and RNA helicase DDX1 recruitment enables coronavirus transition from discontinuous to continuous transcription Cell Host Microbe 16 462 72 25299332 PMC7104987
- [35]Plant EP Dinman JD 2008 The role of programmed −1 ribosomal frameshifting in coronavirus propagation Front Biosci 13 4873 81 18508552 PMC2435135
- [36]Plant EP Sims AC Baric RS Dinman JD Taylor DR 2013 Altering SARS coronavirus frameshift efficiency affects genomic and subgenomic RNA production Viruses 5 279 94 23334702 PMC3564121
- [37]Imbert I Guillemot JC Bourhis JM Bussetta C Coutard B 2006 A second, non-canonical RNA-dependent RNA polymerase in SARS coronavirus EMBO J 25 4933 42 17024178 PMC1618104
- [38]Knoops K Kikkert M Worm SH Zevenhoven-Dobbe JC van der Meer Y 2008 SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum PLOS Biol 6 e226 18798692 PMC2535663
- [39]Gosert R Kanjanahaluethai A Egger D Bienz K Baker SC 2002 RNA replication of mouse hepatitis virus takes place at double-membrane vesicles J Virol 76 3697 708 11907209 PMC136101
- [40]Ulasli M Verheije MH de Haan CA Reggiori F 2010 Qualitative and quantitative ultrastructural analysis of the membrane rearrangements induced by coronavirus Cell Microbiol 12 844 61 20088951 PMC7159092
- [41]Verheije MH Raaben M Mari M te Lintelo EG Reggiori F 2008 Mouse hepatitis coronavirus RNA replication depends on GBF1-mediated ARF1 activation PLOS Pathog 4 e1000088 18551169 PMC2398782
- [42]Stokes HL Baliji S Hui CG Sawicki SG Baker SC Siddell SG 2010 A new cistron in the murine hepatitis virus replicase gene J Virol 84 10148 58 20668085 PMC2937787
- [43]Hagemeijer MC Vonk AM Monastyrska I Rottier PJ de Haan CA 2012 Visualizing coronavirus RNA synthesis in time by using click chemistry J Virol 86 5808 16 22438542 PMC3347275
- [44]den Boon JA Ahlquist P 2010 Organelle-like membrane compartmentalization of positive-strand RNA virus replication factories Annu Rev Microbiol 64 241 56 20825348
- [45]Angelini MM Akhlaghpour M Neuman BW Buchmeier MJ 2013 Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4, and 6 induce double-membrane vesicles mBio 4 e00524 13 PMC3747587 23943763
- [46]Oostra M Hagemeijer MC van Gent M Bekker CP te Lintelo EG 2008 Topology and membrane anchoring of the coronavirus replication complex: Not all hydrophobic domains of nsp3 and nsp6 are membrane spanning J Virol 82 12392 405 18842706 PMC2593338
- [47]Gadlage MJ Sparks JS Beachboard DC Cox RG Doyle JD 2010 Murine hepatitis virus nonstructural protein 4 regulates virus-induced membrane modifications and replication complex function J Virol 84 280 90 19846526 PMC2798404
- [48]Hagemeijer MC Monastyrska I Griffith J van der Sluijs P Voortman J 2014 Membrane rearrangements mediated by coronavirus nonstructural proteins 3 and 4 Virology 458–59 125 35 PMC7111329 24928045
- [49]Maier HJ Hawes PC Cottam EM Mantell J Verkade P 2013 Infectious bronchitis virus generates spherules from zippered endoplasmic reticulum membranes mBio 4 e00801 13 24149513 PMC3812713
- [50]Maier HJ Hawes PC Keep SM Britton P 2014 Spherules and IBV Bioengineered 5 288 92 25482229 PMC4156489
- [51]Hagemeijer MC Rottier PJ de Haan CA 2012 Biogenesis and dynamics of the coronavirus replicative structures Viruses 4 3245 69 23202524 PMC3509692
- [52]Neuman BW Angelini MM Buchmeier MJ 2014 Does form meet function in the coronavirus replicative organelle? Trends Microbiol 22 642 47 25037114 PMC7127430
- [53]Anderson P Kedersha N 2008 Stress granules: the Tao of RNA triage Trends Biochem Sci 33 141 50 18291657
- [54]Kedersha N Stoecklin G Ayodele M Yacono P Lykke-Andersen J 2005 Stress granules and processing bodies are dynamically linked sites of mRNP remodeling J Cell Biol 169 871 84 15967811 PMC2171635
- [55]Ruggieri A Dazert E Metz P Hofmann S Bergeest JP 2012 Dynamic oscillation of translation and stress granule formation mark the cellular response to virus infection Cell Host Microbe 12 71 85 22817989 PMC3873964
- [56]White JP Lloyd RE 2012 Regulation of stress granules in virus systems Trends Microbiol 20 175 83 22405519 PMC3322245
- [57]Reineke LC Lloyd RE 2013 Diversion of stress granules and P-bodies during viral infection Virology 436 255 67 23290869 PMC3611887
- [58]Lindquist ME Lifland AW Utley TJ Santangelo PJ Crowe JE Jr 2010 Respiratory syncytial virus induces host RNA stress granules to facilitate viral replication J Virol 84 12274 84 20844027 PMC2976418
- [59]Raaben M Groot Koerkamp MJ Rottier PJ de Haan CA 2007 Mouse hepatitis coronavirus replication induces host translational shutoff and mRNA decay, with concomitant formation of stress granules and processing bodies Cell Microbiol 9 2218 29 17490409 PMC7162177
- [60]Sola I Galán C Mateos-Gomez PA Palacio L Zuñiga S 2011 The polypyrimidine tract-binding protein affects coronavirus RNA accumulation levels and relocalizes viral RNAs to novel cytoplasmic domains different from replication-transcription sites J Virol 85 5136 49 21411518 PMC3126201
- [61]Emmott E Munday D Bickerton E Britton P Rodgers MA 2013 The cellular interactome of the coronavirus infectious bronchitis virus nucleocapsid protein and functional implications for virus biology J Virol 87 9486 500 23637410 PMC3754094
- [62]Courtney SC Scherbik SV Stockman BM Brinton MA 2012 West Nile virus infections suppress early viral RNA synthesis and avoid inducing the cell stress granule response J Virol 86 3647 57 22258263 PMC3302502
- [63]Onomoto K Yoneyama M Fung G Kato H Fujita T 2014 Antiviral innate immunity and stress granule responses Trends Immunol 35 420 28 25153707 PMC7185371
- [64]Emmott E Rodgers MA Macdonald A McCrory S Ajuh P Hiscox JA 2010 Quantitative proteomics using stable isotope labeling with amino acids in cell culture reveals changes in the cytoplasmic, nuclear, and nucleolar proteomes in Vero cells infected with the coronavirus infectious bronchitis virus Mol Cell Proteomics 9 1920 36 20467043 PMC2938107
- [65]Gustin KE Sarnow P 2006 Positive-strand RNA viruses and the nucleus Viruses and the Nucleus Hiscox JA 161 84 Chichester, UK Wiley
- [66]Wilhelmsen KC Leibowitz JL Bond CW Robb JC 1981 The replication of murine coronaviruses in enucleated cells Virology 110 225 30 6259831 PMC7130927
- [67]Emmett SR Dove B Mahoney L Wurm T Hiscox JA 2005 The cell cycle and virus infection Methods Mol Biol 296 197 218 15576934 PMC7120536
- [68]Surjit M Liu B Chow VT Lal SK 2006 The nucleocapsid protein of severe acute respiratory syndrome-coronavirus inhibits the activity of cyclin-cyclin-dependent kinase complex and blocks S phase progression in mammalian cells J Biol Chem 281 10669 81 16431923 PMC7995956
- [69]Wurm T Chen H Hodgson T Britton P Brooks G Hiscox JA 2001 Localization to the nucleolus is a common feature of coronavirus nucleoproteins, and the protein may disrupt host cell division J Virol 75 9345 56 11533198 PMC114503
- [70]Cawood R Harrison SM Dove BK Reed ML Hiscox JA 2007 Cell cycle dependent nucleolar localization of the coronavirus nucleocapsid protein Cell Cycle 6 863 67 17426449
- [71]Ding L Huang Y Du Q Dong F Zhao X 2014 TGEV nucleocapsid protein induces cell cycle arrest and apoptosis through activation of p53 signaling Biochem Biophys Res Commun 445 497 503 24548406 PMC7092941
- [72]Xu X Zhang H Zhang Q Huang Y Dong J 2013 Porcine epidemic diarrhea virus N protein prolongs S-phase cell cycle, induces endoplasmic reticulum stress, and up-regulates interleukin-8 expression Vet Microbiol 164 212 21 23562137 PMC7117426
- [73]Luo H Chen Q Chen J Chen K Shen X Jiang H 2005 The nucleocapsid protein of SARS coronavirus has a high binding affinity to the human cellular heterogeneous nuclear ribonucleoprotein A1 FEBS Lett 579 2623 28 15862300 PMC7094256
- [74]Shen S Wen ZL Liu DX 2003 Emergence of a coronavirus infectious bronchitis virus mutant with a truncated 3b gene: functional characterization of the 3b protein in pathogenesis and replication Virology 311 16 27 12832199 PMC7125764
- [75]Khan S Fielding BC Tan TH Chou CF Shen S 2006 Over-expression of severe acute respiratory syndrome coronavirus 3b protein induces both apoptosis and necrosis in Vero E6 cells Virus Res 122 20 27 16965829 PMC7114230
- [76]Yuan X Yao Z Shan Y Chen B Yang Z 2005 Nucleolar localization of non-structural protein 3b, a protein specifically encoded by the severe acute respiratory syndrome coronavirus Virus Res 114 70 79 16046244 PMC7114190
- [77]Freundt EC Yu L Park E Lenardo MJ Xu XN 2009 Molecular determinants for subcellular localization of the severe acute respiratory syndrome coronavirus open reading frame 3b protein J Virol 83 6631 40 19403678 PMC2698541
- [78]Matthews KL Coleman CM van der Meer Y Snijder EJ Frieman MB 2014 The ORF4b-encoded accessory proteins of Middle East respiratory syndrome coronavirus and two related bat coronaviruses localize to the nucleus and inhibit innate immune signalling J Gen Virol 95 874 82 24443473 PMC3973478
- [79]Hussain S Gallagher T 2010 SARS-coronavirus protein 6 conformations required to impede protein import into the nucleus Virus Res 153 299 304 20800627 PMC2954772
- [80]Frieman M Yount B Heise M Kopecky-Bromberg SA Palese P Baric RS 2007 Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane J Virol 81 9812 24 17596301 PMC2045396
- [81]Sharma K Akerstrom S Sharma AK Chow VT Teow S 2011 SARS-CoV 9b protein diffuses into nucleus, undergoes active Crm1 mediated nucleocytoplasmic export and triggers apoptosis when retained in the nucleus PLOS ONE 6 e19436 21637748 PMC3103500
- [82]Narayanan K Ramirez SI Lokugamage KG Makino S 2015 Coronavirus nonstructural protein 1: common and distinct functions in the regulation of host and viral gene expression Virus Res 202 89 100 25432065 PMC4444399
- [83]Huang C Lokugamage KG Rozovics JM Narayanan K Semler BL Makino S 2011 Alphacoronavirus transmissible gastroenteritis virus nsp1 protein suppresses protein translation in mammalian cells and in cell-free HeLa cell extracts but not in rabbit reticulocyte lysate J Virol 85 638 43 21047955 PMC3014157
- [84]Li H Zheng Z Zhou P Zhang B Shi Z 2010 The cysteine protease domain of porcine reproductive and respiratory syndrome virus non-structural protein 2 antagonizes interferon regulatory factor 3 activation J Gen Virol 91 2947 58 20826620
- [85]Tijms MA van der Meer Y Snijder EJ 2002 Nuclear localization of non-structural protein 1 and nucleocapsid protein of equine arteritis virus J Gen Virol 83 795 800 11907328
- [86]Burgess HM Gray NK 2012 An integrated model for the nucleo-cytoplasmic transport of cytoplasmic poly(A)-binding proteins Commun Integr Biol 5 243 47 22896784 PMC3419106
- [87]Salaun C MacDonald AI Larralde O Howard L Lochtie K 2010 Poly(A)-binding protein 1 partially relocalizes to the nucleus during herpes simplex virus type 1 infection in an ICP27-independent manner and does not inhibit virus replication J Virol 84 8539 48 20573819 PMC2919032
- [88]Lee C Hodgins D Calvert JG Welch SK Jolie R Yoo D 2006 Mutations within the nuclear localization signal of the porcine reproductive and respiratory syndrome virus nucleocapsid protein attenuate virus replication Virology 346 238 50 16330065 PMC7172752
- [89]Song C Krell P Yoo D 2010 Nonstructural protein 1α subunit-based inhibition of NF-κB activation and suppression of interferon-β production by porcine reproductive and respiratory syndrome virus Virology 407 268 80 20850164
- [90]Han M Du Y Song C Yoo D 2013 Degradation of CREB-binding protein and modulation of type I interferon induction by the zinc finger motif of the porcine reproductive and respiratory syndrome virus nsp1α subunit Virus Res 172 54 65 23287061
- [91]Kim O Sun Y Lai FW Song C Yoo D 2010 Modulation of type I interferon induction by porcine reproductive and respiratory syndrome virus and degradation of CREB-binding protein by non-structural protein 1 in MARC-145 and HeLa cells Virology 402 315 26 20416917 PMC7157927
- [92]Patel D Nan Y Shen M Ritthipichai K Zhu X Zhang YJ 2010 Porcine reproductive and respiratory syndrome virus inhibits type I interferon signaling by blocking STAT1/STAT2 nuclear translocation J Virol 84 11045 55 20739522 PMC2953160
- [93]Chen Z Lawson S Sun Z Zhou X Guan X 2010 Identification of two auto-cleavage products of nonstructural protein 1 (nsp1) in porcine reproductive and respiratory syndrome virus infected cells: nsp1 function as interferon antagonist Virology 398 87 97 20006994 PMC7111964
- [94]Li HP Huang P Park S Lai MMC 1999 Polypyrimidine tract-binding protein binds to the leader RNA of mouse hepatitis virus and serves as a regulator of viral transcription J Virol 73 772 77 9847386 PMC103887
- [95]Galán C Sola I Nogales A Thomas B Akoulitchev A 2009 Host cell proteins interacting with the 3′ end of TGEV coronavirus genome influence virus replication Virology 391 304 14 19580983 PMC7118768
- [96]Choi KS Huang P Lai MM 2002 Polypyrimidine-tract-binding protein affects transcription but not translation of mouse hepatitis virus RNA Virology 303 58 68 12482658
- [97]Choi KS Mizutani A Lai MM 2004 SYNCRIP, a member of the heterogeneous nuclear ribonucleo-protein family, is involved in mouse hepatitis virus RNA synthesis J Virol 78 13153 62 15542667 PMC525026
- [98]Jia J Arif A Ray PS Fox PL 2008 WHEP domains direct noncanonical function of glutamyl-prolyl tRNA synthetase in translational control of gene expression Mol Cell 29 679 90 18374644 PMC2819395
- [101]Madhugiri R Fricke M Marz M Ziebuhr J 2014 RNA structure analysis of alphacoronavirus terminal genome regions Virus Res 194 76 89 25307890 PMC7114417
- [102]Chen SC Olsthoorn RC 2010 Group-specific structural features of the 5′ -proximal sequences of coronavirus genomic RNAs Virology 401 29 41 20202661 PMC7111916
- [103]Kang H Feng M Schroeder ME Giedroc DP Leibowitz JL 2006 Putative cis-acting stem-loops in the 5′ untranslated region of the severe acute respiratory syndrome coronavirus can substitute for their mouse hepatitis virus counterparts J Virol 80 10600 14 16920822 PMC1641749
- [104]Li L Kang H Liu P Makkinje N Williamson ST 2008 Structural lability in stem-loop 1 drives a 5′UTR–3′UTR interaction in coronavirus replication J Mol Biol 377 790 803 18289557 PMC2652258
- [105]Liu P Li L Keane SC Yang D Leibowitz JL Giedroc DP 2009 Mouse hepatitis virus stem-loop 2 adopts a uYNMG(U)a-like tetraloop structure that is highly functionally tolerant of base substitutions J Virol 83 12084 93 19759148 PMC2786756
- [106]Lee CW Li L Giedroc DP 2011 The solution structure of coronaviral stem-loop 2 (SL2) reveals a canonical CUYG tetraloop fold FEBS Lett 585 1049 53 21382373 PMC3086565
- [107]Raman S Bouma P Williams GD Brian DA 2003 Stem-loop III in the 5′ untranslated region is a cis-acting element in bovine coronavirus defective interfering RNA replication J Virol 77 6720 30 12767992 PMC156170
- [108]Yang D Liu P Giedroc DP Leibowitz J 2011 Mouse hepatitis virus stem-loop 4 functions as a spacer element required to drive subgenomic RNA synthesis J Virol 85 9199 209 21715502 PMC3165806
- [109]Goebel SJ Hsue B Dombrowski TF Masters PS 2004 Characterization of the RNA components of a putative molecular switch in the 3′ untranslated region of the murine coronavirus genome J Virol 78 669 82 14694098 PMC368785
- [110]Zust R Miller TB Goebel SJ Thiel V Masters PS 2008 Genetic interactions between an essential 3′ cis-acting RNA pseudoknot, replicase gene products, and the extreme 3′ end of the mouse coronavirus genome J Virol 82 1214 28 Proposes a model for RNA synthesis initiation involving RNA structures and replicase components. 18032506 PMC2224451
- [111]Williams GD Chang RY Brian DA 1999 A phylogenetically conserved hairpin-type 3′ untranslated region pseudoknot functions in coronavirus RNA replication J Virol 73 8349 55 10482585 PMC112852
- [112]Dalton K Casais R Shaw K Stirrups K Evans S 2001 cis-acting sequences required for coronavirus infectious bronchitis virus defective-RNA replication and packaging J Virol 75 125 33 11119581 PMC113905
- [113]Liu Q Johnson RF Leibowitz JL 2001 Secondary structural elements within the 3′ untranslated region of mouse hepatitis virus strain JHM genomic RNA J Virol 75 12105 13 11711601 PMC116106
- [114]Williams AK Wang L Sneed LW Collisson EW 1993 Analysis of a hypervariable region in the 3′ non-coding end of the infectious bronchitis virus genome Virus Res 28 19 27 8388141 PMC7134043
- [115]Goebel SJ Miller TB Bennett CJ Bernard KA Masters PS 2007 A hypervariable region within the 3′ cis-acting element of the murine coronavirus genome is nonessential for RNA synthesis but affects pathogenesis J Virol 81 1274 87 17093194 PMC1797510
- [116]Spagnolo JF Hogue BG 2000 Host protein interactions with the 3′ end of bovine coronavirus RNA and the requirement of the poly(A) tail for coronavirus defective genome replication J Virol 74 5053 65 10799579 PMC110857
- [117]Schelle B Karl N Ludewig B Siddell SG Thiel V 2005 Selective replication of coronavirus genomes that express nucleocapsid protein J Virol 79 6620 30 15890900 PMC1112145
- [118]Ziebuhr J 2005 The coronavirus replicase Coronavirus Replication and Reverse Genetics Enjuanes L 57 94 Berlin Springer-Verlag
- [119]Ulferts R Imbert I Canard B Ziebuhr J 2010 Expression and functions of SARS coronavirus replicative proteins Molecular Biology of the SARS-Coronavirus Lal SK 75 98 Berlin Springer-Verlag
- [120]Gorbalenya AE Enjuanes L Ziebuhr J Snijder EJ 2006 Nidovirales: evolving the largest RNA virus genome Virus Res 117 17 37 16503362 PMC7114179
- [121]Xu X Liu Y Weiss S Arnold E Sarafianos SG Ding J 2003 Molecular model of SARS coronavirus polymerase: implications for biochemical functions and drug design Nucleic Acids Res 31 7117 30 14654687 PMC291860
- [122]Cheng A Zhang W Xie Y Jiang W Arnold E 2005 Expression, purification, and characterization of SARS coronavirus RNA polymerase Virology 335 165 76 15840516 PMC7111802
- [123]Brockway SM Clay CT Lu XT Denison MR 2003 Characterization of the expression, intracellular localization, and replication complex association of the putative mouse hepatitis virus RNA-dependent RNA polymerase J Virol 77 10515 27 12970436 PMC228489
- [124]te Velthuis AJ Arnold JJ Cameron CE van den Worm SH Snijder EJ 2010 The RNA polymerase activity of SARS-coronavirus nsp12 is primer dependent Nucleic Acids Res 38 203 14 19875418 PMC2800238
- [125]Ahn DG Choi JK Taylor DR Oh JW 2012 Biochemical characterization of a recombinant SARS coronavirus nsp12 RNA-dependent RNA polymerase capable of copying viral RNA templates Arch Virol 157 2095 104 22791111 PMC7086750
- [126]te Velthuis AJ van den Worm SH Snijder EJ 2012 The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension Nucleic Acids Res 40 1737 47 22039154 PMC3287201
- [127]Zhai Y Sun F Li X Pang H Xu X 2005 Insights into SARS-CoV transcription and replication from the structure of the nsp7-nsp8 hexadecamer Nat Struct Mol Biol 12 980 86 16228002 PMC7096913
- [128]Imbert I Snijder EJ Dimitrova M Guillemot JC Lecine P Canard B 2008 The SARS-coronavirus PLnc domain of nsp3 as a replication/transcription scaffolding protein Virus Res 133 136 48 18255185 PMC7114086
- [129]Subissi L Posthuma CC Collet A Zevenhoven-Dobbe JC Gorbalenya AE 2014 One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities PNAS 111 E3900 9 Describes the coronavirus core RNA synthesis complex integrating polymerase, proofreading, and capping activities. 25197083 PMC4169972
- [130]Snijder EJ Bredenbeek PJ Dobbe JC Thiel V Ziebuhr J 2003 Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage J Mol Biol 331 991 1004 Comprehensive bioinformatic predictions on the presence of unique enzymatic RNA-modifying activities in coronavirus genomes. 12927536 PMC7159028
- [131]Egloff MP Ferron F Campanacci V Longhi S Rancurel C 2004 The severe acute respiratory syndrome-coronavirus replicative protein nsp9 is a single-stranded RNA-binding subunit unique in the RNA virus world PNAS 101 3792 96 15007178 PMC374323
- [132]Sutton G Fry E Carter L Sainsbury S Walter T 2004 The nsp9 replicase protein of SARS-coronavirus, structure and functional insights Structure 12 341 53 14962394 PMC7135010
- [133]Miknis ZJ Donaldson EF Umland TC Rimmer RA Baric RS Schultz LW 2009 Severe acute respiratory syndrome coronavirus nsp9 dimerization is essential for efficient viral growth J Virol 83 3007 18 19153232 PMC2655571
- [134]Gorbalenya AE Koonin EV Donchenko AP Blinov VM 1989 Coronavirus genome: prediction of putative functional domains in the non-structural polyprotein by comparative amino acid sequence analysis Nucleic Acids Res 17 4847 61 2526320 PMC318036
- [135]Seybert A Posthuma CC van Dinten LC Snijder EJ Gorbalenya AE Ziebuhr J 2005 A complex zinc finger controls the enzymatic activities of nidovirus helicases J Virol 79 696 704 15613297 PMC538568
- [136]Ivanov KA Thiel V Dobbe JC van der Meer Y Snijder EJ Ziebuhr J 2004 Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase J Virol 78 5619 32 15140959 PMC415832
- [137]Seybert A Hegyi A Siddell SG Ziebuhr J 2000 The human coronavirus 229E superfamily 1 helicase has RNA and DNA duplex-unwinding activities with 5′-to-3′ polarity RNA 6 1056 68 10917600 PMC1369980
- [138]Tanner JA Watt RM Chai YB Lu LY Lin MC 2003 The severe acute respiratory syndrome (SARS) coronavirus NTPase/helicase belongs to a distinct class of 5′ to 3′ viral helicases J Biol Chem 278 39578 82 12917423 PMC8060950
- [139]Ivanov KA Ziebuhr J 2004 Human coronavirus 229E nonstructural protein 13: characterization of duplex-unwinding, nucleoside triphosphatase, and RNA 5′-triphosphatase activities J Virol 78 7833 38 15220459 PMC434081
- [140]Lee NR Kwon HM Park K Oh S Jeong YJ Kim DE 2010 Cooperative translocation enhances the unwinding of duplex DNA by SARS coronavirus helicase nsp13 Nucleic Acids Res 38 7626 36 20671029 PMC2995068
- [141]Chen JY Chen WN Poon KM Zheng BJ Lin X 2009 Interaction between SARS-CoV helicase and a multifunctional cellular protein (Ddx5) revealed by yeast and mammalian cell two-hybrid systems Arch Virol 154 507 12 19224332 PMC7087151
- [142]Xu L Khadijah S Fang S Wang L Tay FP Liu DX 2010 The cellular RNA helicase DDX1 interacts with coronavirus nonstructural protein 14 and enhances viral replication J Virol 84 8571 83 20573827 PMC2918985
- [143]Adedeji AO Marchand B te Velthuis AJ Snijder EJ Weiss S 2012 Mechanism of nucleic acid unwinding by SARS-CoV helicase PLOS ONE 7 e36521 22615777 PMC3352918
- [144]Minskaia E Hertzig T Gorbalenya AE Campanacci V Cambillau C 2006 Discovery of an RNA virus 3′→5′ exoribonuclease that is critically involved in coronavirus RNA synthesis PNAS 103 5108 13 16549795 PMC1458802
- [145]Chen Y Cai H Pan J Xiang N Tien P 2009 Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase PNAS 106 3484 89 19208801 PMC2651275
- [146]Denison MR Graham RL Donaldson EF Eckerle LD Baric RS 2011 Coronaviruses: An RNA proofreading machine regulates replication fidelity and diversity RNA Biol 8 270 79 21593585 PMC3127101
- [147]Smith EC Sexton NR Denison MR 2014 Thinking outside the triangle: replication fidelity of the largest RNA viruses Annu Rev Virol 1 111 32 26958717
- [148]Smith EC Denison MR 2012 Implications of altered replication fidelity on the evolution and pathogenesis of coronaviruses Curr Opin Virol 2 519 24 22857992 PMC7102773
- [149]Eckerle LD Becker MM Halpin RA Li K Venter E 2010 Infidelity of SARS-CoV nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing PLOS Pathog 6 e1000896 Describes the relevance of coronavirus ExoN activity in replication fidelity and proofreading mechanisms. 20463816 PMC2865531
- [150]Eckerle LD Lu X Sperry SM Choi L Denison MR 2007 High fidelity of murine hepatitis virus replication is decreased in nsp14 exoribonuclease mutants J Virol 81 12135 44 17804504 PMC2169014
- [151]Bouvet M Imbert I Subissi L Gluais L Canard B Decroly E 2012 RNA 3′-end mismatch excision by the severe acute respiratory syndrome coronavirus nonstructural protein nsp10/nsp14 exoribonuclease complex PNAS 109 9372 77 22635272 PMC3386072
- [152]Smith EC Blanc H Vignuzzi M Denison MR 2013 Coronaviruses lacking exoribonuclease activity are susceptible to lethal mutagenesis: evidence for proofreading and potential therapeutics PLOS Pathog 9 e1003565 23966862 PMC3744431
- [153]Donaldson EF Sims AC Graham RL Denison MR Baric RS 2007 Murine hepatitis virus replicase protein nsp10 is a critical regulator of viral RNA synthesis J Virol 81 6356 68 17392363 PMC1900072
- [154]Bouvet M Lugari A Posthuma CC Zevenhoven JC Bernard S 2014 Coronavirus nsp10, a critical co-factor for activation of multiple replicative enzymes J Biol Chem 289 25783 96 25074927 PMC4162180
- [155]Decroly E Ferron F Lescar J Canard B 2012 Conventional and unconventional mechanisms for capping viral mRNA Nat Rev Microbiol 10 51 65 PMC7097100 22138959
- [156]Bouvet M Debarnot C Imbert I Selisko B Snijder EJ 2010 In vitro reconstitution of SARS-coronavirus mRNA cap methylation PLOS Pathog 6 e1000863 20421945 PMC2858705
- [157]Nogáles A Marquez-Jurado S Galán C Enjuanes L Almazan F 2012 Transmissible gastroenteritis coronavirus RNA-dependent RNA polymerase and nonstructural proteins 2, 3, and 8 are incorporated into viral particles J Virol 86 1261 66 Reports the incorporation of RTC components into coronavirus particles. 22090122 PMC3255853
- [158]Neuman BW Joseph JS Saikatendu KS Serrano P Chatterjee A 2008 Proteomics analysis unravels the functional repertoire of coronavirus nonstructural protein 3 J Virol 82 5279 94 18367524 PMC2395186
- [159]Sims AC Tilton SC Menachery VD Gralinski LE Schafer A 2013 Release of severe acute respiratory syndrome coronavirus nuclear import block enhances host transcription in human lung cells J Virol 87 3885 902 23365422 PMC3624188
- [160]Moshynskyy I Viswanathan S Vasilenko N Lobanov V Petric M 2007 Intracellular localization of the SARS coronavirus protein 9b: evidence of active export from the nucleus Virus Res 127 116 21 17448558 PMC7114319
- [161]Rowland RR Kervin R Kuckleburg C Sperlich A Benfield DA 1999 The localization of porcine reproductive and respiratory syndrome virus nucleocapsid protein to the nucleolus of infected cells and identification of a potential nucleolar localization signal sequence Virus Res 64 1 12 10500278
- Graham R Donalson EF Baric RS 2013 A decade after SARS: strategies for controlling emerging coronaviruses Nat Rev Microbiol 11 836 48 24217413 PMC5147543
- Gralinski LE Baric RS 2015 Molecular pathology of emerging coronavirus infections J Pathol 235 185 95 25270030 PMC4267971
- Lauber C Goeman JJ del Carmen Parquet M Thi Nga P Snijder EJ 2013 The footprint of genome architecture in the largest genome expansion in RNA viruses PLOS Pathog 9 e1003500 23874204 PMC3715407
- Menachery VD Baric RS 2013 Bugs in the system Immunol Rev 255 256 74 23947361 PMC3748621
- Perlman S Netland J 2009 Coronaviruses post-SARS: update on replication and pathogenesis Nat Rev Microbiol 7 439 50 19430490 PMC2830095
Cited by
Sorted by citations
The coding capacity of SARS-CoV-2
Finkel, Y., Mizrahi, O., Nachshon, A., Weingarten-Gabbay, S., Morgenstern, D., Yahalom-Ronen, Y., Tamir, H., Achdout, H., Stein, D., Israeli, O., et al. (2021) · Nature · doi:10.1038/s41586-020-2739-1 · Cited by 644 · see citing works
Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines
Xia, X. (2021) · Vaccines · doi:10.3390/vaccines9070734 · Cited by 201 · see citing works
A Comprehensive Review About SARS-CoV-2
Haque, S. M., Ashwaq, O., Sarief, A., & Azad John Mohamed, A. K. (2020) · Future Virology · doi:10.2217/fvl-2020-0124 · Cited by 121 · see citing works
- Authors
- Sola, I., Almazán, F., Zúñiga, S., & Enjuanes, L.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Venue
- Annual Review of Virology
- Publisher
- Annual Reviews
- Published
- 2015-11-09
- Volume
- 2
- Issue
- 1
- Pages
- 265-288
- ISSN
- 2327-056X (ISSN-L)
- 2327-0578
- PMC
- PMC6025776
- OpenAlex
- W1862727846
- Cited by
- 643
- References
- 1
- Citations by year
- 2026: 45 · 2025: 46 · 2024: 58 · 2023: 68 · 2022: 123 · 2021: 161 · 2020: 114 · 2019: 9 · 2018: 10 · 2017: 4 · 2016: 5
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Virology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- Ministerio de Ciencia e Innovación
- National Institutes of Health (HHSN266200700010C, FP7/2007-2013, CRIP-HHSN266200700010C)
- National Institute of Allergy and Infectious Diseases (P01AI060699)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- coronavirus, RNA synthesis, discontinuous transcription, template switching, 5' untranslated region, cis-acting RNA elements, 5' and 3' untranslated regions, replication-transcription complex, nucleocapsid protein, double-membrane vesicles, proofreading, viral RNA replication
- MeSH terms
- Animals, Humans, RNA, Viral, Transcription, Genetic, Coronavirus, Coronavirus Infections
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review