A complex gene regulatory mechanism that operates at the nexus of multiple RNA processing decisions

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Abstract
Meiosis is a highly conserved and tightly regulated process in which one round of DNA synthesis is followed by two rounds of division. By studying the expression of crs1 pre-mRNA, a meiotic cyclin in fission yeast, Wise and co-workers found that increased RNA accumulation during meiosis is not due to an increase in transcription but rather is a result of RNA processing and turnover. Moreover, they found that polyadenylation of crs1 is linked to splicing, a coupling previously thought to occur only in mammals. They suggest that this highly integrated crs1 regulatory system may allow a rapid response to adverse conditions. Expression of crs1 pre-mRNA, encoding a meiotic cyclin, is blocked in actively growing fission yeast cells by a multifaceted mechanism. The most striking feature is that in vegetative cells, crs1 transcripts are continuously synthesized but are targeted for degradation rather than splicing and polyadenylation. Turnover of crs1 RNA requires the exosome, as do previously described nuclear surveillance and silencing mechanisms, but does not involve a noncanonical poly(A) polymerase. Instead, crs1 transcripts are targeted for destruction by a factor previously implicated in turnover of meiotic RNAs in growing cells. Like exosome mutants, mmi1 mutants splice and polyadenylate vegetative crs1 transcripts. Two regulatory elements are located at the 3′ end of the crs1 gene, consistent with the increased accumulation of spliced RNA in polyadenylation factor mutants. This highly integrated regulatory strategy may ensure a rapid response to adverse conditions, thereby guaranteeing survival.