Abstract
The polyA tails of mRNAs are monitored by the exosome as a quality control mechanism. We find that fission yeast, Schizosaccharomyces pombe, adopts this RNA quality control mechanism to regulate a group of 30 or more meiotic genes at the level of both splicing and RNA turnover. In vegetative cells the RNA binding protein Mmi1 binds to the primary transcripts of these genes. We find the novel motif U(U/C/G)AAAC highly over-represented in targets of Mmi1. Mmi1 can specifically regulate the splicing of particular introns in a transcript: it inhibits the splicing of introns that are in the vicinity of putative Mmi1 binding sites, while allowing the splicing of other introns that are far from such sites. In addition, binding of Mmi1, particularly near the 3' end, alters 3' processing to promote extremely long polyA tails of up to a kilobase. The hyperadenylated transcripts are then targeted for degradation by the nuclear exonuclease Rrp6. The nuclear polyA binding protein Pab2 assists this hyperadenylation-mediated RNA decay. Rrp6 also targets other hyperadenylated transcripts, which become hyperadenylated in an unknown, but Mmi1-independent way. Thus, hyperadenylation may be a general signal for RNA degradation. In addition, binding of Mmi1 can affect the efficiency of 3' cleavage. Inactivation of Mmi1 in meiosis allows meiotic expression, through splicing and RNA stabilization, of at least 29 target genes, which are apparently constitutively transcribed.
Highlights
Gene expression involves intertwined steps of transcription, RNA processing, export and decay [1]
These genes are constitutively transcribed in vegetative cells, but the primary transcripts are not processed into mature mRNAs, but instead are highly unstable
The DSR is a transferable element; if it is deleted from a native gene, the transcript becomes stable in vegetative cells; and if the DSR is added to a heterologous gene, that transcript is destabilized in vegetative cells
Summary
Gene expression involves intertwined steps of transcription, RNA processing, export and decay [1]. One striking example of coordinated gene regulation via RNA processing is found in the fission yeast S. pombe When this yeast enters meiosis, there are at least a dozen meiotic genes that become functionally expressed mainly because of changes in RNA processing [2,3,4,5]. These genes are constitutively transcribed in vegetative cells, but the primary transcripts are not processed into mature mRNAs, but instead are highly unstable. The processing of these transcripts changes dramatically: the RNAs are stabilized, and mature, spliced mRNAs are formed Central to this regulation is the YTH-family RNA binding protein Mmi, which is active in vegetative cells, but inactivated in meiotic cells [3].
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