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XB-ART-57612
Nat Commun January 1, 2020; 11 (1): 5941.

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

Jin L , Chen Y , Crossman DK , Datta A , Vu T , Mobley JA , Basu MK , Scarduzio M , Wang H , Chang C , Datta PK .


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.

PubMed ID: 33230114
PMC ID: PMC7684319
Article link: Nat Commun
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cep57 clk1 homer1 mark3 mmut myc nog npat sag sh2b2 slc22a18 strap
Morpholinos: clk1 MO1 clk1 MO2 strap MO1

Phenotypes: Xla Wt + clk1 MO (ATG) (Fig. 8 g c1r3) [+]

Article Images: [+] show captions
References [+] :
Ahn, SON controls cell-cycle progression by coordinated regulation of RNA splicing. 2011, Pubmed