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Cis-acting replication element

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Background on Cis-acting replication elements (Cre)

Cis-acting replication elements (cre) bring together the 5′ and 3′ ends during replication of positive-sense single-stranded RNA viruses (for example Picornavirus, Flavivirus, Coronavirus, Togaviruses, Hepatitis C virus) and double-stranded RNA viruses (for example rotavirus and reovirus).[1]

Cis-acting replication elements (cre) are regions of the viral RNA that act as regulatory signals for essential steps in the virus life cycle[2].  These regions typically fold into loop-like structures and are located in the protein-making part of the genome called the translated region or flanking these regions in parts of the genome called the untranslated region [2][3].

These folded RNA structures interact with proteins from the virus or host to manage processes like making new viral proteins and replicating the virus’ genetic material [4]. The exact shape and role of these structures vary between different types of viruses [4].

Function of cres in Viral Replication

Positive-Sense RNA Virus Replication

The replication process of some positive-sense RNA viruses (ie. enteroviruses) proceeds via protein-primed replication [5]. This refers to replication that requires the binding of a protein to the RNA to begin [5]. Viral protein genome-linked (VPg) plays the essential role of the protein primer that initiates the replication process in these viruses [5][6]. However, VPg only becomes an active primer when two uridine nucleotides are added to a tyrosine molecule located on the protein [6].The addition of two uridines to a tyrosine molecule is a process called uridylylation [6]. The uridylylation of the tyrosine molecule on VPg is guided by cres [6]. Once the two necessary uridines have been added, VPg is able to prime the initiation of viral replication [6].

Cres also affect viral replication through RNA-RNA interactions, specifically interactions between the cre and other regions of the viral genome [7]. These complex and dynamic interactions are necessary for the efficient synthesis of viral DNA and ensure proper internal ribosome entry site (IRES) function [7]. The IRES allows for the recruitment of host ribosomes and the translation of the viral genome in a cap-independent manner [8]. This is an essential step in viral replication as a lot of positive-sense RNA viruses do not possess the chemical cap on the 5' end of their genome necessary for host ribosomes to translate their RNA into protein [9]. Cap-independent translation bypasses this problem, allowing the virus to generate the proteins it needs for replication.

See also

References

  1. ^ Cordey, S; Gerlach, D; Junier, T; Zdobnov, EM; Kaiser, L; Tapparel, C (2008). "The cis-acting replication elements define human enterovirus and rhinovirus species". RNA. 14 (8): 1568–1578. doi:10.1261/rna.1031408. PMC 2491478. PMID 18541697.
  2. ^ a b Ríos-Marco, Pablo; Romero-López, Cristina; Berzal-Herranz, Alfredo (2016-05-11). "The cis-acting replication element of the Hepatitis C virus genome recruits host factors that influence viral replication and translation". Scientific Reports. 6 (1). doi:10.1038/srep25729. ISSN 2045-2322. PMC 4863150. PMID 27165399.{{cite journal}}: CS1 maint: PMC format (link)
  3. ^ Cordey, Samuel; Gerlach, Daniel; Junier, Thomas; Zdobnov, Evgeny M.; Kaiser, Laurent; Tapparel, Caroline (2008-08). "The cis -acting replication elements define human enterovirus and rhinovirus species". RNA. 14 (8): 1568–1578. doi:10.1261/rna.1031408. ISSN 1355-8382. PMC 2491478. PMID 18541697. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  4. ^ a b Liu, Ying; Wimmer, Eckard; Paul, Aniko V. (2009-09-01). "Cis-acting RNA elements in human and animal plus-strand RNA viruses". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. Structure and Function of Regulatory RNA Elements. 1789 (9): 495–517. doi:10.1016/j.bbagrm.2009.09.007. ISSN 1874-9399. PMC 2783963. PMID 19781674.{{cite journal}}: CS1 maint: PMC format (link)
  5. ^ a b c Warsaba, Reid; Stoynov, Nikolay; Moon, Kyung-Mee; Flibotte, Stephane; Foster, Leonard; Jan, Eric (2022-09-14). López, Susana (ed.). "Multiple Viral Protein Genome-Linked Proteins Compensate for Viral Translation in a Positive-Sense Single-Stranded RNA Virus Infection". Journal of Virology. 96 (17). doi:10.1128/jvi.00699-22. ISSN 0022-538X. PMC 9472611. PMID 35993738.{{cite journal}}: CS1 maint: PMC format (link)
  6. ^ a b c d e Goodfellow, Ian G.; Kerrigan, David; Evans, David J. (2003-01). "Structure and function analysis of the poliovirus cis -acting replication element (CRE)". RNA. 9 (1): 124–137. doi:10.1261/rna.2950603. ISSN 1355-8382. PMC 1370376. PMID 12554882. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  7. ^ a b Ríos-Marco, Pablo; Romero-López, Cristina; Berzal-Herranz, Alfredo (2016-05-11). "The cis-acting replication element of the Hepatitis C virus genome recruits host factors that influence viral replication and translation". Scientific Reports. 6 (1). doi:10.1038/srep25729. ISSN 2045-2322. PMC 4863150. PMID 27165399.{{cite journal}}: CS1 maint: PMC format (link)
  8. ^ Martinez-Salas, Encarnacion; Francisco-Velilla, Rosario; Fernandez-Chamorro, Javier; Embarek, Azman M. (2018-01-04). "Insights into Structural and Mechanistic Features of Viral IRES Elements". Frontiers in Microbiology. 8. doi:10.3389/fmicb.2017.02629. ISSN 1664-302X. PMC 5759354. PMID 29354113.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  9. ^ Rampersad, Sephra; Tennant, Paula (2018-01-01), Tennant, Paula; Fermin, Gustavo; Foster, Jerome E. (eds.), "Chapter 3 - Replication and Expression Strategies of Viruses", Viruses, Academic Press, pp. 55–82, doi:10.1016/b978-0-12-811257-1.00003-6, ISBN 978-0-12-811257-1, PMC 7158166, retrieved 2024-11-24{{citation}}: CS1 maint: PMC format (link)
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