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Translational regulation of viral secretory proteins by the 5′ coding regions and a viral RNA-binding protein
A primary function of 5′ regions in many secretory protein mRNAs is to encode an endoplasmic reticulum (ER) targeting sequence. In this study, we show how the regions coding for the ER-targeting sequences of the influenza glycoproteins NA and HA also function as translational regulatory elements tha...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551715/ https://www.ncbi.nlm.nih.gov/pubmed/28696227 http://dx.doi.org/10.1083/jcb.201702102 |
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author | Nordholm, Johan Petitou, Jeanne Östbye, Henrik da Silva, Diogo V. Dou, Dan Wang, Hao Daniels, Robert |
author_facet | Nordholm, Johan Petitou, Jeanne Östbye, Henrik da Silva, Diogo V. Dou, Dan Wang, Hao Daniels, Robert |
author_sort | Nordholm, Johan |
collection | PubMed |
description | A primary function of 5′ regions in many secretory protein mRNAs is to encode an endoplasmic reticulum (ER) targeting sequence. In this study, we show how the regions coding for the ER-targeting sequences of the influenza glycoproteins NA and HA also function as translational regulatory elements that are controlled by the viral RNA-binding protein (RBP) NS1. The translational increase depends on the nucleotide composition and 5′ positioning of the ER-targeting sequence coding regions and is facilitated by the RNA-binding domain of NS1, which can associate with ER membranes. Inserting the ER-targeting sequence coding region of NA into different 5′ UTRs confirmed that NS1 can promote the translation of secretory protein mRNAs based on the nucleotides within this region rather than the resulting amino acids. By analyzing human protein mRNA sequences, we found evidence that this mechanism of using 5′ coding regions and particular RBPs to achieve gene-specific regulation may extend to human-secreted proteins. |
format | Online Article Text |
id | pubmed-5551715 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-55517152018-02-07 Translational regulation of viral secretory proteins by the 5′ coding regions and a viral RNA-binding protein Nordholm, Johan Petitou, Jeanne Östbye, Henrik da Silva, Diogo V. Dou, Dan Wang, Hao Daniels, Robert J Cell Biol Research Articles A primary function of 5′ regions in many secretory protein mRNAs is to encode an endoplasmic reticulum (ER) targeting sequence. In this study, we show how the regions coding for the ER-targeting sequences of the influenza glycoproteins NA and HA also function as translational regulatory elements that are controlled by the viral RNA-binding protein (RBP) NS1. The translational increase depends on the nucleotide composition and 5′ positioning of the ER-targeting sequence coding regions and is facilitated by the RNA-binding domain of NS1, which can associate with ER membranes. Inserting the ER-targeting sequence coding region of NA into different 5′ UTRs confirmed that NS1 can promote the translation of secretory protein mRNAs based on the nucleotides within this region rather than the resulting amino acids. By analyzing human protein mRNA sequences, we found evidence that this mechanism of using 5′ coding regions and particular RBPs to achieve gene-specific regulation may extend to human-secreted proteins. The Rockefeller University Press 2017-08-07 /pmc/articles/PMC5551715/ /pubmed/28696227 http://dx.doi.org/10.1083/jcb.201702102 Text en © 2017 Nordholm et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Nordholm, Johan Petitou, Jeanne Östbye, Henrik da Silva, Diogo V. Dou, Dan Wang, Hao Daniels, Robert Translational regulation of viral secretory proteins by the 5′ coding regions and a viral RNA-binding protein |
title | Translational regulation of viral secretory proteins by the 5′ coding regions and a viral RNA-binding protein |
title_full | Translational regulation of viral secretory proteins by the 5′ coding regions and a viral RNA-binding protein |
title_fullStr | Translational regulation of viral secretory proteins by the 5′ coding regions and a viral RNA-binding protein |
title_full_unstemmed | Translational regulation of viral secretory proteins by the 5′ coding regions and a viral RNA-binding protein |
title_short | Translational regulation of viral secretory proteins by the 5′ coding regions and a viral RNA-binding protein |
title_sort | translational regulation of viral secretory proteins by the 5′ coding regions and a viral rna-binding protein |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551715/ https://www.ncbi.nlm.nih.gov/pubmed/28696227 http://dx.doi.org/10.1083/jcb.201702102 |
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