Decapping is preceded by 3′ uridylation in a novel pathway of bulk mRNA turnover

Abstract

Turnover of mRNA has mainly been studied in the budding yeast, Saccharomyces cerevisiae, and is thought to be initiated by deadenylation. Now Rissland and Norbury reveal that additional, parallel decay pathways are at work in the fission yeast, Schizosaccharomyces pombe. They find that mRNA decapping is frequently independent of deadenylation and that Cid1-dependent uridylation of polyadenylated mRNAs seems to stimulate decapping as part of a novel mRNA turnover pathway. As human cells contain Cid1 orthologs, uridylation may form the basis of a widespread, conserved mechanism of mRNA decay. Both end structures of eukaryotic mRNAs, namely the 5′ cap and 3′ poly(A) tail, are necessary for transcript stability, and loss of either is sufficient to stimulate decay. mRNA turnover is classically thought to be initiated by deadenylation, as has been particularly well described in Saccharomyces cerevisiae. Here we describe two additional, parallel decay pathways in the fission yeast Schizosaccharomyces pombe. First, in fission yeast mRNA decapping is frequently independent of deadenylation. Second, Cid1-dependent uridylation of polyadenylated mRNAs, such as act1, hcn1 and urg1, seems to stimulate decapping as part of a novel mRNA turnover pathway. Accordingly, urg1 mRNA is stabilized in cid1Δ cells. Uridylation and deadenylation act redundantly to stimulate decapping, and our data suggest that uridylation-dependent decapping is mediated by the Lsm1–7 complex. As human cells contain Cid1 orthologs, uridylation may form the basis of a widespread, conserved mechanism of mRNA decay.