Mechanism of alternative splicing through competing 5’ splice sites
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Alternative splicing of precursor-messenger RNAs (pre-mRNA) bearing introns with competing and overlapping 5’ splice sites (5’SS) produces more mRNAs. We investigated the mechanism of alternative splicing via competing 5’SS by monitoring RNA and protein products of the yeast SRC1/HEH1 gene in different mutant strains. HEH1 alternative splicing requires a sixteen-nucleotide pre-mRNA segment spanning its two 5’SS. The nucleotides are decoded by U5 and U6 small nuclear RNAs (snRNA), supported by specific proteins of the spliceosomal B and Bact complexes, including Prp8. HEH1 alternative splicing became independent of the supporting proteins following recalibration of the pre-mRNA-snRNA base pairings through changes in the 5’SS or U5 and U6 snRNAs. Assisted by proteins that stabilize low-fidelity, high-efficiency spliceosome conformations, the competing HEH1 5’SS are marked for alternative splicing by U5 and U6 snRNAs during B to Bact transition of the spliceosome.
