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

Rissland OS, Norbury CJ - Nat. Struct. Mol. Biol. (2009)

Bottom Line: 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 cid1Delta cells.Uridylation and deadenylation act redundantly to stimulate decapping, and our data suggest that uridylation-dependent decapping is mediated by the Lsm1-7 complex.

View Article: PubMed Central - PubMed

Affiliation: Sir William Dunn School of Pathology, University of Oxford, UK.

ABSTRACT
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 cid1Delta 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.

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Uridylation-mediated decapping requires Lsm1(a, b) Poly(A) tail lengths, binned into groups of ten nt, of capped (a) and decapped (b) act1 sequences isolated from WT [black; n=20 and 40 respectively] and lsm1∆ [white; n=19 and 22 respectively] cells are compared. (c) The percentage of decapped, adenylated act1 sequences that contain [black] or lack [white] terminal uridyl residues is compared for RNA isolated from WT and lsm1∆ cells.
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Figure 7: Uridylation-mediated decapping requires Lsm1(a, b) Poly(A) tail lengths, binned into groups of ten nt, of capped (a) and decapped (b) act1 sequences isolated from WT [black; n=20 and 40 respectively] and lsm1∆ [white; n=19 and 22 respectively] cells are compared. (c) The percentage of decapped, adenylated act1 sequences that contain [black] or lack [white] terminal uridyl residues is compared for RNA isolated from WT and lsm1∆ cells.

Mentions: Previous reports have indicated that the Lsm1-7 complex not only enhances decapping in vivo but also is able to bind oligo(U) tracts in vitro to stimulate decapping34,35. Indeed, previous analysis has shown that the presence of a single terminal uridyl residue was sufficient to stimulate decapping significantly35. We therefore wondered whether the Lsm1-7 complex might mediate uridylation-dependent decapping. We performed act1 cRACE analysis on RNA isolated from lsm1∆ cells. As with dcp1-ts cells, poly(A) tails of capped and decapped act1 mRNAs from lsm1∆ cells were significantly shorter than those from WT cells (p=0.0002 and p=0.0004 respectively; Fig. 7a, b). This is consistent with previous observations in budding yeast that cells lacking Lsm1, like those lacking Dcp1, accumulate deadenylated, capped intermediates34.


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

Rissland OS, Norbury CJ - Nat. Struct. Mol. Biol. (2009)

Uridylation-mediated decapping requires Lsm1(a, b) Poly(A) tail lengths, binned into groups of ten nt, of capped (a) and decapped (b) act1 sequences isolated from WT [black; n=20 and 40 respectively] and lsm1∆ [white; n=19 and 22 respectively] cells are compared. (c) The percentage of decapped, adenylated act1 sequences that contain [black] or lack [white] terminal uridyl residues is compared for RNA isolated from WT and lsm1∆ cells.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2875167&req=5

Figure 7: Uridylation-mediated decapping requires Lsm1(a, b) Poly(A) tail lengths, binned into groups of ten nt, of capped (a) and decapped (b) act1 sequences isolated from WT [black; n=20 and 40 respectively] and lsm1∆ [white; n=19 and 22 respectively] cells are compared. (c) The percentage of decapped, adenylated act1 sequences that contain [black] or lack [white] terminal uridyl residues is compared for RNA isolated from WT and lsm1∆ cells.
Mentions: Previous reports have indicated that the Lsm1-7 complex not only enhances decapping in vivo but also is able to bind oligo(U) tracts in vitro to stimulate decapping34,35. Indeed, previous analysis has shown that the presence of a single terminal uridyl residue was sufficient to stimulate decapping significantly35. We therefore wondered whether the Lsm1-7 complex might mediate uridylation-dependent decapping. We performed act1 cRACE analysis on RNA isolated from lsm1∆ cells. As with dcp1-ts cells, poly(A) tails of capped and decapped act1 mRNAs from lsm1∆ cells were significantly shorter than those from WT cells (p=0.0002 and p=0.0004 respectively; Fig. 7a, b). This is consistent with previous observations in budding yeast that cells lacking Lsm1, like those lacking Dcp1, accumulate deadenylated, capped intermediates34.

Bottom Line: 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 cid1Delta cells.Uridylation and deadenylation act redundantly to stimulate decapping, and our data suggest that uridylation-dependent decapping is mediated by the Lsm1-7 complex.

View Article: PubMed Central - PubMed

Affiliation: Sir William Dunn School of Pathology, University of Oxford, UK.

ABSTRACT
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 cid1Delta 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.

Show MeSH
Related in: MedlinePlus