AI-assisted proofreading of RNA splicing

Guerra Moreno, Ángel; Valcárcel, J. (Juan)

doi:http://dx.doi.org/10.1101/gad.351373.123

AI-assisted proofreading of RNA splicing

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Guerra-Moreno Á, Valcárcel J. AI-assisted proofreading of RNA splicing. Genes Dev. 2023 Dec 26;37(21-24):945-7. DOI: 10.1101/gad.351373.123

Abstract

RNA helicases orchestrate proofreading mechanisms that facilitate accurate intron removal from pre-mRNAs. How these activities are recruited to spliceosome/pre-mRNA complexes remains poorly understood. In this issue of Genes & Development, Zhang and colleagues (pp. 968-983) combine biochemical experiments with AI-based structure prediction methods to generate a model for the interaction between SF3B1, a core splicing factor essential for the recognition of the intron branchpoint, and SUGP1, a protein that bridges SF3B1 with the helicase DHX15. Interaction with SF3B1 exposes the G-patch domain of SUGP1, facilitating binding to and activation of DHX15. The model can explain the activation of cryptic 3' splice sites induced by mutations in SF3B1 or SUGP1 frequently found in cancer.