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Elife. 2018 May 9;7. pii: e37419. doi: 10.7554/eLife.37419.

SRSF3 promotes pluripotency through Nanog mRNA export and coordination of the pluripotency gene expression program.

Author information

1
Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia.
2
Biomedicine Discovery Institute, Development and Stem Cells Program, Monash University, Melbourne, Australia.
3
Australian Regenerative Medicine Institute, Monash University, Clayton, Australia.
4
Bioinformatics Platform, Monash University, Clayton, Australia.
5
School of Biological Sciences, Monash University, Melbourne, Australia.
6
The Francis Crick Institute, London, United Kingdom.
7
Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia.

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.

KEYWORDS:

RNA processing; SR protein; alternative splicing; chromosomes; developmental biology; gene expression; mRNA export; mouse; pluripotent; reprogramming; stem cells

PMID:
29741478
PMCID:
PMC5963917
DOI:
10.7554/eLife.37419
[Indexed for MEDLINE]
Free PMC Article

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