Vaccinia virus D10 has broad decapping activity that is regulated by mRNA splicing.

Autor: Ly M; Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, United States of America., Burgess HM; Department of Microbiology, New York University School of Medicine, New York, New York, United States of America., Shah SB; Center for Computational Biology, University of California Berkeley, Berkeley, California, United States of America., Mohr I; Department of Microbiology, New York University School of Medicine, New York, New York, United States of America., Glaunsinger BA; Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, United States of America.; Department of Plant & Microbial Biology, University of California Berkeley, Berkeley, California, United States of America.; Howard Hughes Medical Institute, Berkeley, California, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2022 Feb 24; Vol. 18 (2), pp. e1010099. Date of Electronic Publication: 2022 Feb 24 (Print Publication: 2022).
DOI: 10.1371/journal.ppat.1010099
Abstrakt: The mRNA 5' cap structure serves both to protect transcripts from degradation and promote their translation. Cap removal is thus an integral component of mRNA turnover that is carried out by cellular decapping enzymes, whose activity is tightly regulated and coupled to other stages of the mRNA decay pathway. The poxvirus vaccinia virus (VACV) encodes its own decapping enzymes, D9 and D10, that act on cellular and viral mRNA, but may be regulated differently than their cellular counterparts. Here, we evaluated the targeting potential of these viral enzymes using RNA sequencing from cells infected with wild-type and decapping mutant versions of VACV as well as in uninfected cells expressing D10. We found that D9 and D10 target an overlapping subset of viral transcripts but that D10 plays a dominant role in depleting the vast majority of human transcripts, although not in an indiscriminate manner. Unexpectedly, the splicing architecture of a gene influences how robustly its corresponding transcript is targeted by D10, as transcripts derived from intronless genes are less susceptible to enzymatic decapping by D10. As all VACV genes are intronless, preferential decapping of transcripts from intron-containing genes provides an unanticipated mechanism for the virus to disproportionately deplete host transcripts and remodel the infected cell transcriptome.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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