Association of yeast Upf1p with direct substrates of the NMD pathway
UMass Chan Affiliations
Department of Molecular Genetics and MicrobiologyDocument Type
Journal ArticlePublication Date
2007-12-19Keywords
Fungal Proteins*Gene Expression Regulation, Fungal
Models, Genetic
Phenotype
Protein Binding
Protein Biosynthesis
RNA Helicases
RNA Stability
RNA, Fungal
RNA, Messenger
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Substrate Specificity
Thiamine
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20872-7. Epub 2007 Dec 17. Link to article on publisher's site
DOI
10.1073/pnas.0709257105Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38480PubMed ID
18087042Related Resources
ae974a485f413a2113503eed53cd6c53
10.1073/pnas.0709257105