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Proc Natl Acad Sci U S A
2003 Oct 14;10021:12081-6. doi: 10.1073/pnas.1635192100.
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DcpS can act in the 5'-3' mRNA decay pathway in addition to the 3'-5' pathway.
van Dijk E
,
Le Hir H
,
Séraphin B
.
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Eukaryotic mRNA degradation proceeds through two main pathways, both involving mRNA cap breakdown. In the 3'-5' mRNA decay pathway, mRNA body degradation generates free m7GpppN that is hydrolyzed by DcpS generating m7GMP. In the 5'-3' pathway, the recently identified human Dcp2 decapping enzyme cleaves the cap of deadenylated mRNAs to produce m7GDP and 5'-phosphorylated mRNA. We investigated mRNA decay in human cell extracts by using a new assay for decapping. We observed that 5'-phosphorylated intermediates resulting from decapping appear after incubation of a substrate RNA in human cell extracts, indicating the presence of an active 5'-3' mRNA decay pathway. Surprisingly, however, the cognate m7GDP product was not detected, whereas abundant amounts of m7GMP were generated. Additional experiments revealed that m7GDP is, unexpectedly, efficiently converted to m7GMP in extracts from various organisms. The factor necessary and sufficient for this reaction was identified as DcpS in both yeast and human. m7GMP is thus a general, pathway-independent, by-product of eukaryotic mRNA decay. m7GDP breakdown should prevent misincorporation of methylated nucleotides in nucleic acids and could generate a unique indicator allowing the cell to monitor mRNA decay.
Anderson,
The 3' to 5' degradation of yeast mRNAs is a general mechanism for mRNA turnover that requires the SKI2 DEVH box protein and 3' to 5' exonucleases of the exosome complex.
1998, Pubmed
Anderson,
The 3' to 5' degradation of yeast mRNAs is a general mechanism for mRNA turnover that requires the SKI2 DEVH box protein and 3' to 5' exonucleases of the exosome complex.
1998,
Pubmed
Banerjee,
5'-terminal cap structure in eucaryotic messenger ribonucleic acids.
1980,
Pubmed
Bashkirov,
A mouse cytoplasmic exoribonuclease (mXRN1p) with preference for G4 tetraplex substrates.
1997,
Pubmed
Beelman,
An essential component of the decapping enzyme required for normal rates of mRNA turnover.
1996,
Pubmed
Bergman,
Analysis of the products of mRNA decapping and 3'-to-5' decay by denaturing gel electrophoresis.
2002,
Pubmed
Caponigro,
Mechanisms and control of mRNA turnover in Saccharomyces cerevisiae.
1996,
Pubmed
Chen,
AU binding proteins recruit the exosome to degrade ARE-containing mRNAs.
2001,
Pubmed
Couttet,
Messenger RNA deadenylylation precedes decapping in mammalian cells.
1997,
Pubmed
Czaplinski,
Should we kill the messenger? The role of the surveillance complex in translation termination and mRNA turnover.
1999,
Pubmed
Daugeron,
The yeast POP2 gene encodes a nuclease involved in mRNA deadenylation.
2001,
Pubmed
Dunckley,
The DCP2 protein is required for mRNA decapping in Saccharomyces cerevisiae and contains a functional MutT motif.
1999,
Pubmed
Frischmeyer,
An mRNA surveillance mechanism that eliminates transcripts lacking termination codons.
2002,
Pubmed
Gao,
A novel mRNA-decapping activity in HeLa cytoplasmic extracts is regulated by AU-rich elements.
2001,
Pubmed
Gera,
Deadenylation-dependent and -independent decay pathways for alpha1-tubulin mRNA in Chlamydomonas reinhardtii.
1998,
Pubmed
Higgs,
Oat phytochrome A mRNA degradation appears to occur via two distinct pathways.
1994,
Pubmed
Hsu,
Yeast cells lacking 5'-->3' exoribonuclease 1 contain mRNA species that are poly(A) deficient and partially lack the 5' cap structure.
1993,
Pubmed
Lee,
Identification and characterization of a human cDNA homologous to yeast SKI2.
1995,
Pubmed
Lennon,
The I.M.A.G.E. Consortium: an integrated molecular analysis of genomes and their expression.
1996,
Pubmed
Lewis,
The influence of 5' and 3' end structures on pre-mRNA metabolism.
1995,
Pubmed
Lim,
Human beta-globin mRNAs that harbor a nonsense codon are degraded in murine erythroid tissues to intermediates lacking regions of exon I or exons I and II that have a cap-like structure at the 5' termini.
1992,
Pubmed
Liu,
The scavenger mRNA decapping enzyme DcpS is a member of the HIT family of pyrophosphatases.
2002,
Pubmed
Lykke-Andersen,
Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay.
2002,
Pubmed
Mitchell,
mRNA turnover.
2001,
Pubmed
Mitchell,
The exosome: a conserved eukaryotic RNA processing complex containing multiple 3'-->5' exoribonucleases.
1997,
Pubmed
Mukherjee,
The mammalian exosome mediates the efficient degradation of mRNAs that contain AU-rich elements.
2002,
Pubmed
Salgado-Garrido,
Sm and Sm-like proteins assemble in two related complexes of deep evolutionary origin.
1999,
Pubmed
Steiger,
Analysis of recombinant yeast decapping enzyme.
2003,
Pubmed
Usher,
On the mechanism of ribonuclease action.
1969,
Pubmed
Wang,
Functional link between the mammalian exosome and mRNA decapping.
2001,
Pubmed
Wang,
The hDcp2 protein is a mammalian mRNA decapping enzyme.
2002,
Pubmed
Wilusz,
The cap-to-tail guide to mRNA turnover.
2001,
Pubmed
van Dijk,
Human Dcp2: a catalytically active mRNA decapping enzyme located in specific cytoplasmic structures.
2002,
Pubmed
van Hoof,
Exosome-mediated recognition and degradation of mRNAs lacking a termination codon.
2002,
Pubmed
van Hoof,
Messenger RNA degradation: beginning at the end.
2002,
Pubmed
