Valentina Botti, François McNicoll, Christina Michaela Steiner, Florian Martin Richter, Anfisa Solovyeva, Marius Wegener, Oliver Daniel Schwich, Ina Poser, Katharina Zarnack, Ilka Wittig, Karla M. Neugebauer, Michaela Müller-McNicoll
- 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.
MetadatenAuthor: | Valentina Botti, François McNicoll, Christina Michaela Steiner, Florian Martin Richter, Anfisa Solovyeva, Marius Wegener, Oliver Daniel Schwich, Ina Poser, Katharina ZarnackORCiDGND, Ilka WittigORCiD, Karla M. Neugebauer, Michaela Müller-McNicollORCiD |
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URN: | urn:nbn:de:hebis:30:3-439094 |
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DOI: | https://doi.org/10.1083/jcb.201610051 |
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ISSN: | 1540-8140 |
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ISSN: | 0021-9525 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/28592444 |
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Parent Title (English): | The journal of cell biology |
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Publisher: | Rockefeller Univ. Press |
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Place of publication: | New York, NY |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2017 |
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Date of first Publication: | 2017/06/07 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2018/01/09 |
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Tag: | Biochemistry; RNA Biology |
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Volume: | 216 |
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Issue: | 7 |
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Page Number: | 17 |
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First Page: | 1993 |
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Last Page: | 2009 |
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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/). |
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HeBIS-PPN: | 427963761 |
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Institutes: | Biowissenschaften / Biowissenschaften |
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| Medizin / Medizin |
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| Exzellenzcluster / Exzellenzcluster Makromolekulare Komplexe |
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Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung-Keine kommerzielle Nutzung-Weitergabe unter gleichen Bedingungen |
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