STRAP regulates alternative splicing fidelity during lineage commitment of mouse embryonic stem cells
Lin Jin,
Yunjia Chen,
David K. Crossman,
Arunima Datta,
Trung Vu,
James A. Mobley,
Malay Kumar Basu,
Mariangela Scarduzio,
Hengbin Wang,
Chenbei Chang and
Pran K. Datta ()
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Lin Jin: University of Alabama at Birmingham
Yunjia Chen: University of Alabama at Birmingham
David K. Crossman: University of Alabama at Birmingham
Arunima Datta: University of Alabama at Birmingham
Trung Vu: University of Alabama at Birmingham
James A. Mobley: University of Alabama at Birmingham
Malay Kumar Basu: University of Alabama at Birmingham
Mariangela Scarduzio: University of Alabama at Birmingham
Hengbin Wang: University of Alabama at Birmingham
Chenbei Chang: University of Alabama at Birmingham
Pran K. Datta: University of Alabama at Birmingham
Nature Communications, 2020, vol. 11, issue 1, 1-18
Abstract:
Abstract Alternative splicing (AS) is involved in cell fate decisions and embryonic development. However, regulation of these processes is poorly understood. Here, we have identified the serine threonine kinase receptor-associated protein (STRAP) as a putative spliceosome-associated factor. Upon Strap deletion, there are numerous AS events observed in mouse embryoid bodies (EBs) undergoing a neuroectoderm-like state. Global mapping of STRAP-RNA binding in mouse embryos by enhanced-CLIP sequencing (eCLIP-seq) reveals that STRAP preferably targets transcripts for nervous system development and regulates AS through preferred binding positions, as demonstrated for two neuronal-specific genes, Nnat and Mark3. We have found that STRAP involves in the assembly of 17S U2 snRNP proteins. Moreover, in Xenopus, loss of Strap leads to impeded lineage differentiation in embryos, delayed neural tube closure, and altered exon skipping. Collectively, our findings reveal a previously unknown function of STRAP in mediating the splicing networks of lineage commitment, alteration of which may be involved in early embryonic lethality in mice.
Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19698-6
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DOI: 10.1038/s41467-020-19698-6
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