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Publication : STRAP regulates alternative splicing fidelity during lineage commitment of mouse embryonic stem cells.

First Author  Jin L Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  5941
PubMed ID  33230114 Mgi Jnum  J:299860
Mgi Id  MGI:6490747 Doi  10.1038/s41467-020-19698-6
Citation  Jin L, et al. (2020) STRAP regulates alternative splicing fidelity during lineage commitment of mouse embryonic stem cells. Nat Commun 11(1):5941
abstractText  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.
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