Cellular differentiation state modulates the mRNA export activity of SR proteins

SR proteins function in nuclear pre-mRNA processing, mRNA export, and translation. To investigate their cellular dynamics, we developed a quantitative assay, which detects differences in nucleocytoplasmic shuttling among
SR proteins function in nuclear pre-mRNA processing, mRNA export, and translation. To investigate their cellular dynamics, we developed a quantitative assay, which detects differences in nucleocytoplasmic shuttling among seven canonical SR protein family members. As expected, SRSF2 and SRSF5 shuttle poorly in HeLa cells but surprisingly display considerable shuttling in pluripotent murine P19 cells. Combining individual-resolution cross-linking and immunoprecipitation (iCLIP) and mass spectrometry, we show that elevated arginine methylation of SRSF5 and lower phosphorylation levels of cobound SRSF2 enhance shuttling of SRSF5 in P19 cells by modulating protein-protein and protein-RNA interactions. Moreover, SRSF5 is bound to pluripotency-specific transcripts such as Lin28a and Pou5f1/Oct4 in the cytoplasm. SRSF5 depletion reduces and overexpression increases their cytoplasmic mRNA levels, suggesting that enhanced mRNA export by SRSF5 is required for the expression of pluripotency factors. Remarkably, neural differentiation of P19 cells leads to dramatically reduced SRSF5 shuttling. Our findings indicate that posttranslational modification of SR proteins underlies the regulation of their mRNA export activities and distinguishes pluripotent from differentiated cells.
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Metadaten
Author:Valentina Botti, François McNicoll, Christina Michaela Steiner, Florian Martin Richter, Anfisa Solovyeva, Marius Wegener, Oliver D. Schwich, Ina Poser, Kathi Zarnack, Ilka Wittig, Karla M. Neugebauer, Michaela Müller-McNicoll
URN:urn:nbn:de:hebis:30:3-439094
DOI:http://dx.doi.org/10.1083/jcb.201610051
ISSN:1540-8140
ISSN:0021-9525
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=28592444
Parent Title (English):The journal of cell biology
Publisher:Rockefeller Univ. Press
Place of publication:New York, NY
Document Type:Article
Language:English
Year of Completion:2017
Date of first Publication:2017/06/07
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/01/09
Tag:Biochemistry; RNA Biology
Volume:216
Issue:7
Pagenumber:17
First Page:1993
Last Page:2009
Note:
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/).
HeBIS PPN:427963761
Institutes:Biowissenschaften
Medizin
Exzellenzcluster Makromolekulare Komplexe
Dewey Decimal Classification:570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Keine kommerzielle Nutzung-Weitergabe unter gleichen Bedingungen

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