Kaposi's sarcoma-associated herpesvirus ORF57 protein protects viral transcripts from specific nuclear RNA decay pathways by preventing hMTR4 recruitment.

PLoS Pathogens
Julio C RuizNicholas K Conrad

Abstract

Nuclear RNAs are subject to a number of RNA decay pathways that serve quality control and regulatory functions. As a result, any virus that expresses its genes in the nucleus must have evolved mechanisms that avoid these pathways, but the how viruses evade nuclear RNA decay remains largely unknown. The multifunctional Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 (Mta) protein is required for the nuclear stability of viral transcripts. In the absence of ORF57, we show that viral transcripts are subject to degradation by two specific nuclear RNA decay pathways, PABPN1 and PAPα/γ-mediated RNA decay (PPD) in which decay factors are recruited through poly(A) tails, and an ARS2-mediated RNA decay pathway dependent on the 5' RNA cap. In transcription pulse chase assays, ORF57 appears to act primarily by inhibiting the ARS2-mediated RNA decay pathway. In the context of viral infection in cultured cells, inactivation of both decay pathways by RNAi is necessary for the restoration of ORF57-dependent viral genes produced from an ORF57-null bacmid. Mechanistically, we demonstrate that ORF57 protects viral transcripts by preventing the recruitment of the exosome co-factor hMTR4. In addition, our data suggest that ORF57 recruitment o...Continue Reading

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Citations

Nov 13, 2019·Wiley Interdisciplinary Reviews. RNA·William Garland, Torben Heick Jensen
Sep 18, 2020·Viruses·Daniel Macveigh-FierroMandy Muller
Oct 10, 2020·Trends in Biochemical Sciences·Xavier Rambout, Lynne E Maquat
May 6, 2021·ELife·Anna M ScarboroughNicholas K Conrad

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Methods Mentioned

BETA
flow cytometry
immunoprecipitation
RIP
CLIP
co-immunoprecipitation
electrophoresis
transfection
transfecting
PCR
transfections

Software Mentioned

ImageQuant
ImageStudio

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