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Translational regulation of viral secretory proteins by the 5 ' coding regions and a viral RNA-binding protein
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
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Number of Authors: 7
2017 (English)In: Journal of Cell Biology, ISSN 0021-9525, E-ISSN 1540-8140, Vol. 216, no 8, 2283-2293 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2017. Vol. 216, no 8, 2283-2293 p.
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-147141DOI: 10.1083/jcb.201702102ISI: 000407078100011PubMedID: 28696227OAI: oai:DiVA.org:su-147141DiVA: diva2:1144087
Available from: 2017-09-25 Created: 2017-09-25 Last updated: 2017-09-25Bibliographically approved

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Nordholm, JohanÖstbye, Henrikda Silva, Diogo V.Dou, DanWang, HaoDaniels, Robert
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