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Non-Canonical Translation Initiation Mechanisms Employed by Eukaryotic Viral mRNAs.
Sorokin, Ivan I; Vassilenko, Konstantin S; Terenin, Ilya M; Kalinina, Natalia O; Agol, Vadim I; Dmitriev, Sergey E.
  • Sorokin II; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234, Russia.
  • Vassilenko KS; Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia.
  • Terenin IM; Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141701, Russia.
  • Kalinina NO; Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia.
  • Agol VI; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234, Russia.
  • Dmitriev SE; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234, Russia.
Biochemistry (Mosc) ; 86(9): 1060-1094, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1416611
ABSTRACT
Viruses exploit the translation machinery of an infected cell to synthesize their proteins. Therefore, viral mRNAs have to compete for ribosomes and translation factors with cellular mRNAs. To succeed, eukaryotic viruses adopt multiple strategies. One is to circumvent the need for m7G-cap through alternative instruments for ribosome recruitment. These include internal ribosome entry sites (IRESs), which make translation independent of the free 5' end, or cap-independent translational enhancers (CITEs), which promote initiation at the uncapped 5' end, even if located in 3' untranslated regions (3' UTRs). Even if a virus uses the canonical cap-dependent ribosome recruitment, it can still perturb conventional ribosomal scanning and start codon selection. The pressure for genome compression often gives rise to internal and overlapping open reading frames. Their translation is initiated through specific mechanisms, such as leaky scanning, 43S sliding, shunting, or coupled termination-reinitiation. Deviations from the canonical initiation reduce the dependence of viral mRNAs on translation initiation factors, thereby providing resistance to antiviral mechanisms and cellular stress responses. Moreover, viruses can gain advantage in a competition for the translational machinery by inactivating individual translational factors and/or replacing them with viral counterparts. Certain viruses even create specialized intracellular "translation factories", which spatially isolate the sites of their protein synthesis from cellular antiviral systems, and increase availability of translational components. However, these virus-specific mechanisms may become the Achilles' heel of a viral life cycle. Thus, better understanding of the unconventional mechanisms of viral mRNA translation initiation provides valuable insight for developing new approaches to antiviral therapy.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Peptide Chain Initiation, Translational / RNA, Messenger / RNA, Viral / Eukaryotic Cells Limits: Animals / Humans Language: English Journal: Biochemistry (Mosc) Year: 2021 Document Type: Article Affiliation country: S0006297921090042

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Peptide Chain Initiation, Translational / RNA, Messenger / RNA, Viral / Eukaryotic Cells Limits: Animals / Humans Language: English Journal: Biochemistry (Mosc) Year: 2021 Document Type: Article Affiliation country: S0006297921090042