Ratnadiwakara, M;
Archer, SK;
Dent, CI;
De Los Mozos, IR;
Beilharz, TH;
Knaupp, AS;
Nefzger, CM;
... Anko, M-L; + view all
(2018)
SRSF3 promotes pluripotency through Nanog mRNA export and coordination of the pluripotency gene expression program.
ELIFE
, 7
, Article e37419. 10.7554/eLife.37419.001.
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Abstract
The establishment and maintenance of pluripotency depend on precise coordination of gene expression. We establish serine-arginine-rich splicing factor 3 (SRSF3) as an essential regulator of RNAs encoding key components of the mouse pluripotency circuitry, SRSF3 ablation resulting in the loss of pluripotency and its overexpression enhancing reprogramming. Strikingly, SRSF3 binds to the core pluripotency transcription factor Nanog mRNA to facilitate its nucleo-cytoplasmic export independent of splicing. In the absence of SRSF3 binding, Nanog mRNA is sequestered in the nucleus and protein levels are severely downregulated. Moreover, SRSF3 controls the alternative splicing of the export factor Nxf1 and RNA regulators with established roles in pluripotency, and the steady-state levels of mRNAs encoding chromatin modifiers. Our investigation links molecular events to cellular functions by demonstrating how SRSF3 regulates the pluripotency genes and uncovers SRSF3-RNA interactions as a critical means to coordinate gene expression during reprogramming, stem cell self-renewal and early development.
| Type: | Article |
|---|---|
| Title: | SRSF3 promotes pluripotency through Nanog mRNA export and coordination of the pluripotency gene expression program |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/eLife.37419.001 |
| Publisher version: | http://doi.org/10.7554/eLife.37419.001 |
| Language: | English |
| Additional information: | Copyright © Ratnadiwakara et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10050478 |
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