The Smaug family of sequence-specific RNA binding proteins regulates mRNA translation and degradation by binding to consensus stem-loop structures in target mRNAs. Vts1p is a member of the Smaug protein family that regulates the stability of target transcripts in Saccharomyces cerevisiae. Here we focus on the mechanism of Vts1p-mediated mRNA decay. Using RNA reporters that recapitulate Vts1p-mediated decay in vivo, we demonstrate that Vts1p stimulates mRNA degradation through deadenylation mediated by the Ccr4p-Pop2p-Not deadenylase complex. We also show that Vts1p interacts with the Ccr4p-Pop2p-Not complex suggesting that Vts1p recruits the Ccr4p-Pop2p-Not deadenylase complex to target mRNAs, resulting in transcript decay. Following deadenylation Vts1p target transcripts are decapped and subsequently degraded by the 5'-to-3' exonuclease Xrn1p. Decapping and 5'-to-3' decay is thought to occur in foci known as P-bodies, and we provide evidence that Vts1p function may involve P-bodies. Taken together with previous work, these data suggest that Smaug family members employ a conserved mechanism to induce transcript degradation that involves recruitment of the Ccr4-Pop2-Not deadenylase to target mRNAs.

• PMID: 18469165
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Journal Article | Research Support, Non-U.S. Gov't

Authors

Rendl LM, Bieman MA, Smibert CA

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