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Vaccinia virus D10 has broad decapping activity that is regulated by mRNA splicing
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903303/ https://www.ncbi.nlm.nih.gov/pubmed/35202449 http://dx.doi.org/10.1371/journal.ppat.1010099 |
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author | Ly, Michael Burgess, Hannah M. Shah, Sahil B. Mohr, Ian Glaunsinger, Britt A. |
author_facet | Ly, Michael Burgess, Hannah M. Shah, Sahil B. Mohr, Ian Glaunsinger, Britt A. |
author_sort | Ly, Michael |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8903303 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-89033032022-03-09 Vaccinia virus D10 has broad decapping activity that is regulated by mRNA splicing Ly, Michael Burgess, Hannah M. Shah, Sahil B. Mohr, Ian Glaunsinger, Britt A. PLoS Pathog Research Article 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. Public Library of Science 2022-02-24 /pmc/articles/PMC8903303/ /pubmed/35202449 http://dx.doi.org/10.1371/journal.ppat.1010099 Text en © 2022 Ly et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Ly, Michael Burgess, Hannah M. Shah, Sahil B. Mohr, Ian Glaunsinger, Britt A. Vaccinia virus D10 has broad decapping activity that is regulated by mRNA splicing |
title | Vaccinia virus D10 has broad decapping activity that is regulated by mRNA splicing |
title_full | Vaccinia virus D10 has broad decapping activity that is regulated by mRNA splicing |
title_fullStr | Vaccinia virus D10 has broad decapping activity that is regulated by mRNA splicing |
title_full_unstemmed | Vaccinia virus D10 has broad decapping activity that is regulated by mRNA splicing |
title_short | Vaccinia virus D10 has broad decapping activity that is regulated by mRNA splicing |
title_sort | vaccinia virus d10 has broad decapping activity that is regulated by mrna splicing |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903303/ https://www.ncbi.nlm.nih.gov/pubmed/35202449 http://dx.doi.org/10.1371/journal.ppat.1010099 |
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