TY  - JOUR
A1  - Botti, Valentina
A1  - McNicoll, François
A1  - Steiner, Christina Michaela
A1  - Richter, Florian Martin
A1  - Solovyeva, Anfisa
A1  - Wegener, Marius
A1  - Schwich, Oliver Daniel
A1  - Poser, Ina
A1  - Zarnack, Katharina
A1  - Wittig, Ilka
A1  - Neugebauer, Karla M.
A1  - Müller-McNicoll, Michaela
T1  - Cellular differentiation state modulates the mRNA export activity of SR proteins
T2  - The journal of cell biology
N2  - 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.
KW  - RNA Biology
KW  - Biochemistry
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/43909
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-439094
SN  - 1540-8140
SN  - 0021-9525
N1  - 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/).
VL  - 216
IS  - 7
SP  - 1993
EP  - 2009
PB  - Rockefeller Univ. Press
CY  - New York, NY
ER  -