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Co-regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing
Three of the eight RNA segments encoded by the influenza A virus (IAV) undergo alternative splicing to generate distinct proteins. Previously, we found that host proteins hnRNP K and NS1-BP regulate IAV M segment splicing, but the mechanistic details were unknown. Here we show NS1-BP and hnRNP K bin...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008300/ https://www.ncbi.nlm.nih.gov/pubmed/29921878 http://dx.doi.org/10.1038/s41467-018-04779-4 |
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author | Thompson, Matthew G. Muñoz-Moreno, Raquel Bhat, Prasanna Roytenberg, Renat Lindberg, John Gazzara, Matthew R. Mallory, Michael J. Zhang, Ke García-Sastre, Adolfo Fontoura, Beatriz M. A. Lynch, Kristen W. |
author_facet | Thompson, Matthew G. Muñoz-Moreno, Raquel Bhat, Prasanna Roytenberg, Renat Lindberg, John Gazzara, Matthew R. Mallory, Michael J. Zhang, Ke García-Sastre, Adolfo Fontoura, Beatriz M. A. Lynch, Kristen W. |
author_sort | Thompson, Matthew G. |
collection | PubMed |
description | Three of the eight RNA segments encoded by the influenza A virus (IAV) undergo alternative splicing to generate distinct proteins. Previously, we found that host proteins hnRNP K and NS1-BP regulate IAV M segment splicing, but the mechanistic details were unknown. Here we show NS1-BP and hnRNP K bind M mRNA downstream of the M2 5′ splice site (5′ss). NS1-BP binds most proximal to the 5′ss, partially overlapping the U1 snRNP binding site, while hnRNP K binds further downstream and promotes U1 snRNP recruitment. Mutation of either or both the hnRNP K and NS1-BP-binding sites results in M segment mis-splicing and attenuated IAV replication. Additionally, we show that hnRNP K and NS1-BP regulate host splicing events and that viral infection causes mis-splicing of some of these transcripts. Therefore, our proposed mechanism of hnRNP K/NS1-BP mediated IAV M splicing provides potential targets of antiviral intervention and reveals novel host functions for these proteins. |
format | Online Article Text |
id | pubmed-6008300 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60083002018-06-21 Co-regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing Thompson, Matthew G. Muñoz-Moreno, Raquel Bhat, Prasanna Roytenberg, Renat Lindberg, John Gazzara, Matthew R. Mallory, Michael J. Zhang, Ke García-Sastre, Adolfo Fontoura, Beatriz M. A. Lynch, Kristen W. Nat Commun Article Three of the eight RNA segments encoded by the influenza A virus (IAV) undergo alternative splicing to generate distinct proteins. Previously, we found that host proteins hnRNP K and NS1-BP regulate IAV M segment splicing, but the mechanistic details were unknown. Here we show NS1-BP and hnRNP K bind M mRNA downstream of the M2 5′ splice site (5′ss). NS1-BP binds most proximal to the 5′ss, partially overlapping the U1 snRNP binding site, while hnRNP K binds further downstream and promotes U1 snRNP recruitment. Mutation of either or both the hnRNP K and NS1-BP-binding sites results in M segment mis-splicing and attenuated IAV replication. Additionally, we show that hnRNP K and NS1-BP regulate host splicing events and that viral infection causes mis-splicing of some of these transcripts. Therefore, our proposed mechanism of hnRNP K/NS1-BP mediated IAV M splicing provides potential targets of antiviral intervention and reveals novel host functions for these proteins. Nature Publishing Group UK 2018-06-19 /pmc/articles/PMC6008300/ /pubmed/29921878 http://dx.doi.org/10.1038/s41467-018-04779-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Thompson, Matthew G. Muñoz-Moreno, Raquel Bhat, Prasanna Roytenberg, Renat Lindberg, John Gazzara, Matthew R. Mallory, Michael J. Zhang, Ke García-Sastre, Adolfo Fontoura, Beatriz M. A. Lynch, Kristen W. Co-regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing |
title | Co-regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing |
title_full | Co-regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing |
title_fullStr | Co-regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing |
title_full_unstemmed | Co-regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing |
title_short | Co-regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing |
title_sort | co-regulatory activity of hnrnp k and ns1-bp in influenza and human mrna splicing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008300/ https://www.ncbi.nlm.nih.gov/pubmed/29921878 http://dx.doi.org/10.1038/s41467-018-04779-4 |
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