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Role of RNA chaperones in virus replication.

ABSTRACT: RNA molecules are functionally diverse in part due to their extreme structural flexibility that allows rapid regulation by refolding. RNA folding could be a difficult process as often molecules adopt a spatial conformation that is very stable but not biologically functional, named a kinetic trap. RNA chaperones are non-specific RNA binding proteins that help RNA folding by resolving misfolded structures or preventing their formation. There is a large number of viruses whose genome is RNA that allows some evolutionary advantages, such as rapid genome mutation. On the other hand, regions of the viral RNA genomes can adopt different structural conformations, some of them lacking functional relevance and acting as misfolded intermediates. In fact, for an efficient replication, they often require RNA chaperone activities. There is a growing list of RNA chaperones encoded by viruses involved in different steps of the viral cycle. Also, cellular RNA chaperones have been involved in replication of RNA viruses. This review briefly describes RNA chaperone activities and is focused in the roles that viral or cellular nucleic acid chaperones have in RNA virus replication, particularly in those viruses that require discontinuous RNA synthesis.

SUBMITTER: Zuniga S

PROVIDER: S-EPMC7114511 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Role of RNA chaperones in virus replication.

Zúñiga Sonia S Sola Isabel I Cruz Jazmina L G JL Enjuanes Luis L

Virus research 20080808 2

RNA molecules are functionally diverse in part due to their extreme structural flexibility that allows rapid regulation by refolding. RNA folding could be a difficult process as often molecules adopt a spatial conformation that is very stable but not biologically functional, named a kinetic trap. RNA chaperones are non-specific RNA binding proteins that help RNA folding by resolving misfolded structures or preventing their formation. There is a large number of viruses whose genome is RNA that al ...[more]

PMID: 18675859

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Project description:Human bocavirus 1 (HBoV1) belongs to the species Primate bocaparvovirus of the genus Bocaparvovirus of the Parvoviridae family. HBoV1 causes acute respiratory tract infections in young children and has a selective tropism for the apical surface of well-differentiated human airway epithelia (HAE). In this study, we identified an additional HBoV1 gene, bocavirus-transcribed small noncoding RNA (BocaSR), within the 3' noncoding region (nucleotides [nt] 5199 to 5338) of the viral genome of positive sense. BocaSR is transcribed by RNA polymerase III (Pol III) from an intragenic promoter at levels similar to that of the capsid protein-coding mRNA and is essential for replication of the viral DNA in both transfected HEK293 and infected HAE cells. Mechanistically, we showed that BocaSR regulates the expression of HBoV1-encoded nonstructural proteins NS1, NS2, NS3, and NP1 but not NS4. BocaSR is similar to the adenovirus-associated type I (VAI) RNA in terms of both nucleotide sequence and secondary structure but differs from it in that its regulation of viral protein expression is independent of RNA-activated protein kinase (PKR) regulation. Notably, BocaSR accumulates in the viral DNA replication centers within the nucleus and likely plays a direct role in replication of the viral DNA. Our findings reveal BocaSR to be a novel viral noncoding RNA that coordinates the expression of viral proteins and regulates replication of viral DNA within the nucleus. Thus, BocaSR may be a target for antiviral therapies for HBoV and may also have utility in the production of recombinant HBoV vectors.IMPORTANCE Human bocavirus 1 (HBoV1) is pathogenic to humans, causing acute respiratory tract infections in young children. In this study, we identified a novel HBoV1 gene that lies in the 3' noncoding region of the viral positive-sense genome and is transcribed by RNA polymerase III into a noncoding RNA of 140 nt. This bocavirus-transcribed small RNA (BocaSR) diverges from both adenovirus-associated (VA) RNAs and Epstein-Barr virus-encoded small RNAs (EBERs) with respect to RNA sequence, representing a third species of this kind of Pol III-dependent viral noncoding RNA and the first noncoding RNA identified in autonomous parvoviruses. Unlike the VA RNAs, BocaSR localizes to the viral DNA replication centers of the nucleus and is essential for expression of viral nonstructural proteins independent of RNA-activated protein kinase R and replication of HBoV1 genomes. The identification of BocaSR and its role in virus DNA replication reveals potential avenues for developing antiviral therapies.

Dataset Information

Role of RNA chaperones in virus replication.

Publications

Role of RNA chaperones in virus replication.

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