Identification and characterization of novel factors that act in the nonsense-mediated mRNA decay pathway in nematodes, flies and mammals
Nonsense‐mediated mRNA decay (NMD) is a surveillance mechanism that degrades mRNAs harboring premature termination codons (PTCs). We have conducted a genome‐wide RNAi screen in Caenorhabditis elegans that resulted in the identification of five novel NMD genes that are conserved throughout evolution....
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Published in | EMBO reports Vol. 16; no. 1; pp. 71 - 78 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Blackwell Publishing Ltd
01.01.2015
Nature Publishing Group UK BlackWell Publishing Ltd |
Subjects | |
Online Access | Get full text |
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Summary: | Nonsense‐mediated mRNA decay (NMD) is a surveillance mechanism that degrades mRNAs harboring premature termination codons (PTCs). We have conducted a genome‐wide RNAi screen in
Caenorhabditis elegans
that resulted in the identification of five novel NMD genes that are conserved throughout evolution. Two of their human homologs,
GNL2
(
ngp‐1
) and
SEC13
(
npp‐20
), are also required for NMD in human cells. We also show that the
C. elegans
gene
noah‐2
, which is present in
Drosophila melanogaster
but absent in humans, is an NMD factor in fruit flies. Altogether, these data identify novel NMD factors that are conserved throughout evolution, highlighting the complexity of the NMD pathway and suggesting that yet uncovered novel factors may act to regulate this process.
Synopsis
A genome‐wide RNAi screen in
C. elegans
identifies five novel NMD genes that are required for development and conserved throughout evolution, suggesting that the regulation of the NMD pathway is more complex than previously thought.
Five novel NMD factors that are also essential for development are identified in
C. elegans
.
Two of the human orthologs,
GNL2
(
ngp‐1
) and
SEC13
(
npp‐20
), are also required for NMD in human cells.
The
C. elegans
gene
noah‐2
, which is present in
Drosophila melanogaster
but absent in humans, is a tissue‐specific NMD factor in fruit flies.
Graphical Abstract
A genome‐wide RNAi screen in
C. elegans
identifies five novel NMD genes that are required for development and conserved throughout evolution, suggesting that the regulation of the NMD pathway is more complex than previously thought. |
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Bibliography: | Supplementary Figure S1Supplementary Figure S2Supplementary Figure S3Supplementary Figure S4Supplementary InformationReview Process File istex:784E9B4CE77C75431DAD1D00AB92E3488B615EA5 ark:/67375/WNG-LQ7L7LSS-8 MRC core funding Wellcome Trust - No. 095518/Z/11/Z; No. 098410/Z/12/Z ArticleID:EMBR201439183 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Subject Categories RNA Biology |
ISSN: | 1469-221X 1469-3178 |
DOI: | 10.15252/embr.201439183 |