Cross talk between the upstream exon-intron junction and Prp2 facilitates splicing of non-consensus introns

Splicing of mRNA precursors is essential in the regulation of gene expression. U2AF65 recognizes the poly-pyrimidine tract and helps in the recognition of the branch point. Inactivation of fission yeast U2AF65 (Prp2) blocks splicing of most, but not all, pre-mRNAs, for reasons that are not understood. Here, we have determined genome-wide the splicing efficiency of fission yeast cells as they progress into synchronous meiosis in the presence or absence of functional Prp2. Our data indicate that in addition to the splicing elements at the 3' end of any intron, the nucleotides immediately upstream the intron will determine whether Prp2 is required or dispensable for splicing. By changing those nucleotides in any given intron, we regulate its Prp2 dependency. Our results suggest a model in which Prp2 is required for the coordinated recognition of both intronic ends, placing Prp2 as a key regulatory element in the determination of the exon-intron boundaries.This work was supported by grants from the Spanish Ministerio de Economia y Competitividad (MINECO) (BFU2015-66347-P and BFU2018-PGC2018-097248-B-I00), PLAN E and Feder, MEIONet (BFU2015-71786-REDT), and Unidad de Excelencia María de Maeztu (CEX2018-000792-M). E.H. is recipient of an ICREA Academia Award (Generalitat de Catalunya)