Negative control contributes to an extensive program of meiotic splicing in fission yeast.

Despite a high frequency of introns in the fission yeast Schizosaccharomyces pombe, regulated splicing is virtually unknown. We present evidence that splicing constitutes a major mechanism for controlling gene expression during meiosis, as 12 of 96 transcripts tested, which encode known components as well as previously uncharacterized ORFs, retain introns until specific times during differentiation. The meiotically spliced pre-mRNAs include two cyclins, rem1 (discovered by Ayte and Nurse) and crs1. Consistent with the use of regulated splicing to block protein production, expression of crs1 in vegetative cells is toxic. Analyses of gene chimeras indicate that splicing is prevented in mitotically growing cells via inhibition, in contrast to the positive control of meiotic splicing in budding yeast. Most strikingly, splicing of crs1 and rem1 is regulated by sequences located outside the coding regions, far from the target introns, a phenomenon previously observed only in metazoans.