Mutations in U1 snRNA bypass the requirement for a cell type-specific RNA splicing factor.

Previous studies have demonstrated that efficient splicing of the primary transcript of the yeast MER2 gene requires the MER1 protein, which is produced only in meiotic cells. A genetic selection was devised to recover second-site mutations that bypass the requirement for MER1 in MER2 RNA-splicing. This selection identified a mutation in SNR19, the gene for U1 snRNA. The suppressor mutation affects the first residue in U1 snRNA, allowing this nucleotide to base pair with the eighth nucleotide in the MER2 intron. This base in MER2 lies outside the conserved hexanucleotide that defines the 5' splice site in yeast. The MER2 5' splice site (GUUCGU) differs from the consensus in yeast (GUAYGU) at the third position. When this nucleotide is mutated to restore the consensus, base pairing with U1 snRNA is increased and the requirement for MER1 is alleviated.