RNA-Protein Interactome at the Hepatitis E Virus Internal Ribosome Entry Site.

Autor:	Kumar S; Virology Laboratory, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, India., Verma R; Virology Laboratory, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, India., Saha S; Laboratory of Functional Proteomics, Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad, India., Agrahari AK; Noncommunicable Disease Group, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, India., Shukla S; Virology Laboratory, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, India., Singh ON; Virology Laboratory, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, India., Berry U; Virology Laboratory, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, India., Anurag; Virology Laboratory, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, India., Maiti TK; Laboratory of Functional Proteomics, Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad, India., Asthana S; Noncommunicable Disease Group, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, India., Ranjith-Kumar CT; University School of Biotechnology, Guru Gobind Singh Indraprastha University, New Delhi, India., Surjit M; Virology Laboratory, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, India.
Jazyk:	angličtina
Zdroj:	Microbiology spectrum [Microbiol Spectr] 2023 Aug 17; Vol. 11 (4), pp. e0282722. Date of Electronic Publication: 2023 Jun 29.
DOI:	10.1128/spectrum.02827-22
Abstrakt:	Multiple processes exist in a cell to ensure continuous production of essential proteins either through cap-dependent or cap-independent translation processes. Viruses depend on the host translation machinery for viral protein synthesis. Therefore, viruses have evolved clever strategies to use the host translation machinery. Earlier studies have shown that genotype 1 hepatitis E virus (g1-HEV) uses both cap-dependent and cap-independent translation machineries for its translation and proliferation. Cap-independent translation in g1-HEV is driven by an 87-nucleotide-long RNA element that acts as a noncanonical, internal ribosome entry site-like (IRESl) element. Here, we have identified the RNA-protein interactome of the HEV IRESl element and characterized the functional significance of some of its components. Our study identifies the association of HEV IRESl with several host ribosomal proteins, demonstrates indispensable roles of ribosomal protein RPL5 and DHX9 (RNA helicase A) in mediating HEV IRESl activity, and establishes the latter as a bona fide internal translation initiation site. IMPORTANCE Protein synthesis is a fundamental process for survival and proliferation of all living organisms. The majority of cellular proteins are produced through cap-dependent translation. Cells also use a variety of cap-independent translation processes to synthesize essential proteins during stress. Viruses depend on the host cell translation machinery to synthesize their own proteins. Hepatitis E virus (HEV) is a major cause of hepatitis worldwide and has a capped positive-strand RNA genome. Viral nonstructural and structural proteins are synthesized through a cap-dependent translation process. An earlier study from our laboratory reported the presence of a fourth open reading frame (ORF) in genotype 1 HEV, which produces the ORF4 protein using a cap-independent internal ribosome entry site-like (IRESl) element. In the current study, we identified the host proteins that associate with the HEV-IRESl RNA and generated the RNA-protein interactome. Through a variety of experimental approaches, our data prove that HEV-IRESl is a bona fide internal translation initiation site. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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