Structure and function of RNA elements present in enteroviral genomes
Enteroviruses are small RNA(+) viruses that encode one open reading frame flanked by two extensive noncoding regions carrying structural RNA regulatory elements that control replication and translation processes. For a long time the central, coding region was thought to remain single-stranded and its only function was supposed to be as the template for polyprotein synthesis. It turned out, however, that the protein coding region also encodes important RNA structures crucial for the viral life cycle and virus persistence in host cells. This review considers the RNA structures in enteroviral genomes identified and characterized to date.
Balvay L, Soto Rifo R, Ricci EP, Decimo D, Ohlmann T (2009) Structural and functional diversity of viral IRESes. Biochim Biophys Acta 1789: 542-557. doi: 10.1016/j.bbagrm.2009.07.005
Banerjee R, Echeverri A, Dasgupta A, (1997) Poliovirus-encoded 2C polypeptide specifically binds to the 3’-terminal sequences of viral negative-strand RNA. J.Virol. 71, 9570–9578.
Banerjee R, Dasgupta A, (2001a). Interaction of picornavirus 2C polypeptide with the viral negative-strand RNA. J. Gen. Virol. 82, 2621–2627.
Banerjee R, Dasgupta A, (2001b). Specific interaction of hepatitis C virus protease/helicase NS3 with the 3’-terminal sequences of viral positive- and negative-strand RNA. J. Virol. 75, 1708–1721.
Barton DJ, O'Donnell BJ, Flanegan JB (2001) 5' cloverleaf in poliovirus RNA is a cis-acting replication element required for negative-strand synthesis. EMBO J 20: 1439-1448. doi: 10.1093/emboj/20.6.1439
Bhattacharyya S, Das S (2005) Mapping of secondary structure of the spacer region within the 5'-untranslated region of the coxsackievirus B3 RNA: possible role of an apical GAGA loop in binding La protein and influencing internal initiation of translation. Virus Res 108: 89-100. doi: 10.1016/j.virusres.2004.08.020
Brunner JE, Nguyen JHC, Roehl HH, Ho TV, Swiderek KM, Semler BL (2005). Functional interaction of heterogeneous nuclear ribonucleoprotein C with poliovirus RNA synthesis initiation complexes. J. Virol. 79, 3254–3266.
Burrill CP, Westesson O, Schulte MB, Strings VR, Segal M, Andino R (2013) Global RNA structure analysis of poliovirus identifies a conserved RNA structure involved in viral replication and infectivity. J Virol 87: 11670-11683. doi: 10.1128/JVI.01560-13
Chakrabarti A, Jha BK, Silverman RH (2011) New insights into the role of RNase L in innate immunity. J Interferon Cytokine Res 31: 49-57. doi: 10.1089/jir.2010.0120
Claridge JK, Headey SJ, Chow JY, Schwalbe M, Edwards PJ, Jeffries CM, Venugopal H, Trewhella J, Pascal SM (2009) A picornaviral loop-to-loop replication complex. J Struct Biol 166: 251-262. doi: 10.1016/j.jsb.2009.02.010
Dutkiewicz M, Ojdowska A, Gorska A, Swiatkowska A, Ciesiolka J (2014) The structural and phylogenetic profile of the 3' terminus of coxsackievirus B3 negative strand. Virus Res 188: 81-89. doi: 10.1016/j.virusres.2014.03.020
Dutkiewicz MS, A. Ojdowska, A. Smolska, B. Dymarek-Babs, T. Jasinska, A. Ciesiolka, J. (2012) Molecular mechnisms of genome expression of coxsackievirus B3 that belongs to enteroviruses. BioTechnologia 414-423doi: 10.5114/bta.2012.46595
Ertel KJ, Brunner JE, Semler BL, 2010. Mechanistic consequences of hnRNP C binding to both RNA termini of poliovirus negative-strand RNA intermediates. J. Virol. 84, 4229–4242.
Fernandez-Miragall O, Lopez de Quinto S, Martinez-Salas E (2009) Relevance of RNA structure for the activity of picornavirus IRES elements. Virus Res 139: 172-182. doi: 10.1016/j.virusres.2008.07.009
Filbin ME, Kieft JS (2009) Toward a structural understanding of IRES RNA function. Curr Opin Struct Biol 19: 267-276. doi: 10.1016/j.sbi.2009.03.005
Garmaroudi FS, Marchant D, Hendry R, Luo H, Yang D, Ye X, Shi J, McManus BM (2015) Coxsackievirus B3 replication and pathogenesis. Future Microbiol 10: 629-653. doi: 10.2217/fmb.15.5
Goodfellow I, Chaudhry Y, Richardson A, Meredith J, Almond JW, Barclay W, Evans DJ. (2000) Identification of a cis-acting replication element within the poliovirus coding region. J Virol.; 74:4590–4600.
Han JQ, Townsend HL, Jha BK, Paranjape JM, Silverman RH, Barton DJ (2007) A phylogenetically conserved RNA structure in the poliovirus open reading frame inhibits the antiviral endoribonuclease RNase L. J Virol 81: 5561-5572. doi: 10.1128/jvi.01857-06
Jackowiak P, Figlerowicz M, Kurzynska-Kokorniak A, Figlerowicz M (2011) Mechanisms involved in the development of chronic hepatitis C as potential targets of antiviral therapy. Curr Pharm Biotechnol 12: 1774-1780. doi:
Li ZH, Nagy PD (2011). Diverse roles of host RNA-binding proteins in RNA virus replication. RNA Biol. 8, 305–315.
Liu Y, Wimmer E, Paul AV (2009) Cis-acting RNA elements in human and animal plus-strand RNA viruses. Biochim Biophys Acta 1789: 495-517. doi: 10.1016/j.bbagrm.2009.09.007
Lozano G, Martinez-Salas E (2015) Structural insights into viral IRES-dependent translation mechanisms. Curr Opin Virol 12: 113-120. doi: 10.1016/j.coviro.2015.04.008
Mehndiratta MM, Mehndiratta P, Pande R (2014) Poliomyelitis: historical facts, epidemiology, and current challenges in eradication. Neurohospitalist 4: 223-229. doi: 10.1177/1941874414533352
Muehlenbachs A, Bhatnagar J, Zaki SR (2015) Tissue tropism, pathology and pathogenesis of enterovirus infection. J Pathol 235: 217-228. doi: 10.1002/path.4438
Ooij MJ, Glaudemans DH, Heus HA, Kuppeveld FJ, Melchers WJ (2006a) Structural and functional integrity of the coxsackievirus B3 oriR: spacing between coaxial RNA helices. J. Gen. Virol. 87: 689-695.
Ooij MJ, Polacek C, Glaudemans DH, Kuijpers J, Kuppeveld FJ, Andino R, Agol VI, Melchers WJ (2006b) Polyadenylation of genomic RNA and initiation of antigenomic RNA in a positive-strand RNA virus are controlled by the same cis-element. Nucl. Acids Res. 34: 2953-2965.
Pelletier J, Sonenberg N. (1988) Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature 334: 320-325.
Racaniello VR, (2007). Picornaviridae: the virus and their replication. In: Knipe, H.P.,Howley, D.M. (Eds.), Field’s Virology. , 5th ed. Lippincott Williams & Wilkins a Wolter Kulwer Business, pp. 795–838.
Semler BL (2004) Poliovirus proves IRES-istible in vivo. J Clin Invest 113: 1678-1681. doi: 10.1172/jci22139
Sharma N, Ogram SA, Morasco BJ, Spear A, Chapman NM, Flanegan JB (2009) Functional role of the 5' terminal cloverleaf in Coxsackievirus RNA replication. Virology 393: 238-249. doi: 10.1016/j.virol.2009.07.039
Sean P, Semler BL, (2008). Coxsackievirus B RNA replication: lessons from poliovirus. In: Tracy, S., Oberste, M.S., Drescher, K. (Eds.), Group B Coxsackieviruses. Springer, Berlin, Heidelberg, pp. 89–121.
Song Y, Liu Y, Ward CB, Mueller S, Futcher B, Skiena S, Paul AV, Wimmer E (2012) Identification of two functionally redundant RNA elements in the coding sequence of poliovirus using computer-generated design. Proc Natl Acad Sci U S A 109: 14301-14307. doi: 10.1073/pnas.1211484109
Steil BP, Barton DJ (2009) Cis-active RNA elements (CREs) and picornavirus RNA replication. Virus Res 139: 240-252. doi: 10.1016/j.virusres.2008.07.027
Townsend HL, Jha BK, Han JQ, Maluf NK, Silverman RH, Barton DJ (2008a) A viral RNA competitively inhibits the antiviral endoribonuclease domain of RNase L. Rna 14: 1026-1036. doi: 10.1261/rna.958908
Townsend HL, Jha BK, Silverman RH, Barton DJ (2008b) A putative loop E motif and an H-H kissing loop interaction are conserved and functional features in a group C enterovirus RNA that inhibits ribonuclease L. RNA Biol 5: 263-272. doi:
van der Linden L, Wolthers KC, van Kuppeveld FJ (2015) Replication and Inhibitors of Enteroviruses and Parechoviruses. Viruses 7: 4529-4562. doi: 10.3390/v7082832
Vogt DA, Andino R (2010) An RNA element at the 5'-end of the poliovirus genome functions as a general promoter for RNA synthesis. PLoS Pathog 6: e1000936. doi: 10.1371/journal.ppat.1000936
Witwer C, Rauscher S, Hofacker IL, Stadler PF (2001) Conserved RNA secondary structures in Picornaviridae genomes. Nucleic Acids Res 29: 5079-5089. doi:
Zoll J, Heus HA, van Kuppeveld FJ, Melchers WJ (2009) The structure-function relationship of the enterovirus 3'-UTR. Virus Res 139: 209-216. doi: 10.1016/j.virusres.2008.07.014
Acta Biochimica Polonica is an open access quarterly and publishes four issues a year. All contents are distributed under the Creative Commons Attribution-ShareAlike 4.0 International (CC BY-SA 4.0) license. Everybody may use the content following terms: Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made, ShareAlike — If you remix, transform, or build upon the material, you must distribute your contributions under the same license as the original. There are no additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Copyright for all published papers © stays with the authors.
Copyright for the journal: © Polish Biochemical Society.