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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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Decapped mRNAs are often uridylated(a) The percentage of decapped, adenylated cRACE products that contain terminal uridyl residues is shown for act1, adh1, gar2, hcn1, pof9 and urg1 (n= 10/40, 4/16, 5/11, 3/12, 2/8 and 7/39 respectively). (b) The poly(A) tail lengths of non-uridylated [black] and uridylated [white] decapped urg1 RNAs were binned into groups of ten nt. Tail lengths were then plotted as the percentage of adenylated species. (c) The poly(A) tail lengths of all non-uridylated [black; 31 sequences] and uridylated [white; 95 sequences] decapped transcripts are compared. For each transcript, each tail length was normalized to the median of non-uridylated tail length to correct for inter-transcript poly(A) tail length variability. These normalized lengths were then binned into groups and plotted as the percentage of adenylated species. (d) As in (b), the poly(A) tail lengths of non-uridylated [black] and uridylated [white] decapped act1 (b) were binned into groups of ten nt. Tail lengths were then plotted as the percentage of adenylated species.
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Figure 2: Decapped mRNAs are often uridylated(a) The percentage of decapped, adenylated cRACE products that contain terminal uridyl residues is shown for act1, adh1, gar2, hcn1, pof9 and urg1 (n= 10/40, 4/16, 5/11, 3/12, 2/8 and 7/39 respectively). (b) The poly(A) tail lengths of non-uridylated [black] and uridylated [white] decapped urg1 RNAs were binned into groups of ten nt. Tail lengths were then plotted as the percentage of adenylated species. (c) The poly(A) tail lengths of all non-uridylated [black; 31 sequences] and uridylated [white; 95 sequences] decapped transcripts are compared. For each transcript, each tail length was normalized to the median of non-uridylated tail length to correct for inter-transcript poly(A) tail length variability. These normalized lengths were then binned into groups and plotted as the percentage of adenylated species. (d) As in (b), the poly(A) tail lengths of non-uridylated [black] and uridylated [white] decapped act1 (b) were binned into groups of ten nt. Tail lengths were then plotted as the percentage of adenylated species.

Mentions: One to two non-templated 3′ terminal uridyl residues were found on 25% of the polyadenylated, decapped act1 transcripts (Fig. 2a), suggesting a role for uridylation in a novel mRNA decay pathway. No terminal uridyl residues were observed on non-adenylated products. Similarly, terminal uridyl residues were found on 18% of decapped, adenylated urg1 messages, 25% of decapped, adenylated hcn1, adh1 and pof9 messages and 45% of decapped, adenylated gar2 messages (Fig. 2a). Uridylation thus appears to be a widespread mRNA modification in S. pombe. In contrast, no terminal uridyl residues were observed on 22 S. cerevisiae act1 cRACE products analyzed (p=0.005, Supplementary Fig. 2b online). This finding is consistent with the observation that budding yeast does not contain a Cid1 ortholog12,20.


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

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

Decapped mRNAs are often uridylated(a) The percentage of decapped, adenylated cRACE products that contain terminal uridyl residues is shown for act1, adh1, gar2, hcn1, pof9 and urg1 (n= 10/40, 4/16, 5/11, 3/12, 2/8 and 7/39 respectively). (b) The poly(A) tail lengths of non-uridylated [black] and uridylated [white] decapped urg1 RNAs were binned into groups of ten nt. Tail lengths were then plotted as the percentage of adenylated species. (c) The poly(A) tail lengths of all non-uridylated [black; 31 sequences] and uridylated [white; 95 sequences] decapped transcripts are compared. For each transcript, each tail length was normalized to the median of non-uridylated tail length to correct for inter-transcript poly(A) tail length variability. These normalized lengths were then binned into groups and plotted as the percentage of adenylated species. (d) As in (b), the poly(A) tail lengths of non-uridylated [black] and uridylated [white] decapped act1 (b) were binned into groups of ten nt. Tail lengths were then plotted as the percentage of adenylated species.
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getmorefigures.php?uid=PMC2875167&req=5

Figure 2: Decapped mRNAs are often uridylated(a) The percentage of decapped, adenylated cRACE products that contain terminal uridyl residues is shown for act1, adh1, gar2, hcn1, pof9 and urg1 (n= 10/40, 4/16, 5/11, 3/12, 2/8 and 7/39 respectively). (b) The poly(A) tail lengths of non-uridylated [black] and uridylated [white] decapped urg1 RNAs were binned into groups of ten nt. Tail lengths were then plotted as the percentage of adenylated species. (c) The poly(A) tail lengths of all non-uridylated [black; 31 sequences] and uridylated [white; 95 sequences] decapped transcripts are compared. For each transcript, each tail length was normalized to the median of non-uridylated tail length to correct for inter-transcript poly(A) tail length variability. These normalized lengths were then binned into groups and plotted as the percentage of adenylated species. (d) As in (b), the poly(A) tail lengths of non-uridylated [black] and uridylated [white] decapped act1 (b) were binned into groups of ten nt. Tail lengths were then plotted as the percentage of adenylated species.
Mentions: One to two non-templated 3′ terminal uridyl residues were found on 25% of the polyadenylated, decapped act1 transcripts (Fig. 2a), suggesting a role for uridylation in a novel mRNA decay pathway. No terminal uridyl residues were observed on non-adenylated products. Similarly, terminal uridyl residues were found on 18% of decapped, adenylated urg1 messages, 25% of decapped, adenylated hcn1, adh1 and pof9 messages and 45% of decapped, adenylated gar2 messages (Fig. 2a). Uridylation thus appears to be a widespread mRNA modification in S. pombe. In contrast, no terminal uridyl residues were observed on 22 S. cerevisiae act1 cRACE products analyzed (p=0.005, Supplementary Fig. 2b online). This finding is consistent with the observation that budding yeast does not contain a Cid1 ortholog12,20.

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