Association of yeast Upf1p with direct substrates of the NMD pathway
(2007) In Proceedings of the National Academy of Sciences of the United States of America 104(52). p.7-20872- Abstract
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that detects and degrades transcripts containing premature translation termination codons. Gene expression profiling experiments have shown that inactivation of the NMD pathway leads to the accumulation of both aberrant, nonsense-containing mRNAs, and many apparently wild-type transcripts. Such increases in transcript steady-state levels could arise from direct changes in the respective mRNA half-lives, or indirectly, as a consequence of the stabilization of transcripts encoding specific regulatory proteins. Here, we distinguished direct from indirect substrates by virtue of their association with the Saccharomyces cerevisiae Upf1 protein. Analyses of this dataset, and its... (More)
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that detects and degrades transcripts containing premature translation termination codons. Gene expression profiling experiments have shown that inactivation of the NMD pathway leads to the accumulation of both aberrant, nonsense-containing mRNAs, and many apparently wild-type transcripts. Such increases in transcript steady-state levels could arise from direct changes in the respective mRNA half-lives, or indirectly, as a consequence of the stabilization of transcripts encoding specific regulatory proteins. Here, we distinguished direct from indirect substrates by virtue of their association with the Saccharomyces cerevisiae Upf1 protein. Analyses of this dataset, and its comparison to the sets of transcripts that respectively increase or decrease in abundance when NMD is either inactivated or reactivated, indicate that the number of direct NMD substrates is larger than previously thought and that low abundance, alternatively transcribed mRNAs, i.e., mRNAs whose 5' ends are derived from previously unannotated 5' flanking sequences, comprise a significant class of direct substrates. Using thiamine metabolism as an example, we also show that apparent NMD-regulated cellular pathways may actually reflect the detection of low-abundance alternative transcripts under conditions where a pathway is repressed.
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- author
- Johansson, Marcus J O LU ; He, Feng ; Spatrick, Phyllis ; Li, Chunfang and Jacobson, Allan
- publishing date
- 2007-12-26
- type
- Contribution to journal
- publication status
- published
- keywords
- Fungal Proteins, Gene Expression Regulation, Fungal, Models, Genetic, Phenotype, Protein Binding, Protein Biosynthesis, RNA Helicases/metabolism, RNA Stability, RNA, Fungal/genetics, RNA, Messenger/metabolism, Saccharomyces cerevisiae/genetics, Saccharomyces cerevisiae Proteins/metabolism, Substrate Specificity, Thiamine/chemistry
- in
- Proceedings of the National Academy of Sciences of the United States of America
- volume
- 104
- issue
- 52
- pages
- 7 - 20872
- publisher
- National Academy of Sciences
- external identifiers
-
- scopus:38049103286
- pmid:18087042
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.0709257105
- language
- English
- LU publication?
- no
- id
- bb1a3213-2069-4bba-b169-32719432719a
- date added to LUP
- 2024-03-05 16:54:25
- date last changed
- 2024-03-06 07:56:45
@article{bb1a3213-2069-4bba-b169-32719432719a,
abstract = {{<p>Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that detects and degrades transcripts containing premature translation termination codons. Gene expression profiling experiments have shown that inactivation of the NMD pathway leads to the accumulation of both aberrant, nonsense-containing mRNAs, and many apparently wild-type transcripts. Such increases in transcript steady-state levels could arise from direct changes in the respective mRNA half-lives, or indirectly, as a consequence of the stabilization of transcripts encoding specific regulatory proteins. Here, we distinguished direct from indirect substrates by virtue of their association with the Saccharomyces cerevisiae Upf1 protein. Analyses of this dataset, and its comparison to the sets of transcripts that respectively increase or decrease in abundance when NMD is either inactivated or reactivated, indicate that the number of direct NMD substrates is larger than previously thought and that low abundance, alternatively transcribed mRNAs, i.e., mRNAs whose 5' ends are derived from previously unannotated 5' flanking sequences, comprise a significant class of direct substrates. Using thiamine metabolism as an example, we also show that apparent NMD-regulated cellular pathways may actually reflect the detection of low-abundance alternative transcripts under conditions where a pathway is repressed.</p>}},
author = {{Johansson, Marcus J O and He, Feng and Spatrick, Phyllis and Li, Chunfang and Jacobson, Allan}},
issn = {{1091-6490}},
keywords = {{Fungal Proteins; Gene Expression Regulation, Fungal; Models, Genetic; Phenotype; Protein Binding; Protein Biosynthesis; RNA Helicases/metabolism; RNA Stability; RNA, Fungal/genetics; RNA, Messenger/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae Proteins/metabolism; Substrate Specificity; Thiamine/chemistry}},
language = {{eng}},
month = {{12}},
number = {{52}},
pages = {{7--20872}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences of the United States of America}},
title = {{Association of yeast Upf1p with direct substrates of the NMD pathway}},
url = {{http://dx.doi.org/10.1073/pnas.0709257105}},
doi = {{10.1073/pnas.0709257105}},
volume = {{104}},
year = {{2007}},
}