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

Madara Ratnadiwakara, Stuart K Archer, Craig I Dent, Igor Ruiz De Los Mozos, Traude H Beilharz, Anja S Knaupp, Christian M Nefzger, Jose M Polo, Minna-Liisa Anko

Research output: Contribution to journalArticleResearchpeer-review

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.
LanguageEnglish
JournaleLife
DOIs
StateAccepted/In press - 2018

Cite this

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title = "SRSF3 promotes pluripotency through Nanog mRNA export and coordination of the pluripotency gene expression program",
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.",
author = "Madara Ratnadiwakara and Archer, {Stuart K} and Dent, {Craig I} and {Ruiz De Los Mozos}, Igor and Beilharz, {Traude H} and Knaupp, {Anja S} and Nefzger, {Christian M} and Polo, {Jose M} and Minna-Liisa Anko",
year = "2018",
doi = "10.7554/eLife.37419",
language = "English",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

SRSF3 promotes pluripotency through Nanog mRNA export and coordination of the pluripotency gene expression program. / Ratnadiwakara, Madara; Archer, Stuart K; Dent, Craig I; Ruiz De Los Mozos, Igor; Beilharz, Traude H; Knaupp, Anja S; Nefzger, Christian M; Polo, Jose M; Anko, Minna-Liisa.

In: eLife, 2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - SRSF3 promotes pluripotency through Nanog mRNA export and coordination of the pluripotency gene expression program

AU - Ratnadiwakara,Madara

AU - Archer,Stuart K

AU - Dent,Craig I

AU - Ruiz De Los Mozos,Igor

AU - Beilharz,Traude H

AU - Knaupp,Anja S

AU - Nefzger,Christian M

AU - Polo,Jose M

AU - Anko,Minna-Liisa

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.7554/eLife.37419

DO - 10.7554/eLife.37419

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JO - eLife

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SN - 2050-084X

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