Fig. 8: Cell-type specific splicing complexes confer distinct vulnerabilities to PB. | Nature Communications

Fig. 8: Cell-type specific splicing complexes confer distinct vulnerabilities to PB.

From: Determination of trunk neural crest cell fate and susceptibility to splicing perturbation by the DLC1-SF3B1-PHF5A splicing complex

Fig. 8: Cell-type specific splicing complexes confer distinct vulnerabilities to PB.

a The schematic diagram illustrates the binding of the NC-specific DLC1 to intronic motifs of SOX9 and SNAI2 pre-mRNA, along with the splicing factors SF3B1-PHF5A, which recognize the BS sequence to form a BP-A pocket. The DLC1-SF3B1-PHF5A complex is required for regulating the splicing of SOX9 and SNAI2 pre-mRNA in specifying prospective NCCs. However, this complex also increases the vulnerability of NCCs to the splicing modulator PB, which competitively inhibits the recognition of BS sequence by SF3B1-PHF5A. This inhibition occurs in both SOX9 intron 2 and SNAI2 intron 1, due to their shorter in length and weaker Py tract, resulting in intron retention and loss of NC progenitors. In contrast, the SLU7-SF3B1-PHF5A complex regulates splicing of SOX9 and SNAI2 pre-mRNAs in somites, imparting resistance to splicing perturbation by PB. Py polypyrimidine.

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