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An internal open reading frame triggers nonsense‐mediated decay of the yeast SPT10 mRNA
Author(s) -
Welch Ellen M.,
Jacobson Allan
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.21.6134
Subject(s) - biology , nonsense mediated decay , messenger rna , open reading frame , p bodies , translation (biology) , microbiology and biotechnology , translational frameshift , mutant , upstream open reading frame , gene , saccharomyces cerevisiae , nonsense mutation , mutation , genetics , rna , rna splicing , peptide sequence , missense mutation
Yeast cells containing a temperature‐sensitive mutation in the PRT1 gene were found to selectively stabilize mRNAs harboring early nonsense codons. The similarities between the mRNA decay phenotypes of prt1‐1 cells and those lacking the nonsense‐mediated mRNA decay (NMD) factor Upf1p led us to determine whether both types of mutations cause the accumulation of the same mRNAs. Differential display analysis and mRNA half‐life measurements demonstrated that the HHF2 mRNA increased in abundance in prt1‐1 and upf1 Δ cells, but did not manifest a change in decay rate. In both mutant strains this increase was attributable to stabilization of the SPT10 transcript, an mRNA encoding a transcriptional regulator of HHF2 . Analyses of chimeric mRNAs used to identify the cis ‐acting basis for NMD of the SPT10 mRNA indicated that ribosomes scan beyond its initiator AUG and initiate at the next downstream AUG, resulting in premature translation termination. By searching a yeast database for transcripts with sequence features similar to those of the SPT10 mRNA, other transcripts that decay by the NMD pathway were identified. Our results demonstrate that mRNAs undergoing leaky scanning are a new class of endogenous NMD substrate, and suggest the existence of a novel cellular regulatory circuit.