mRNA destabilization triggered by premature translational termination depends on at least three cis-acting sequence elements and one trans-acting factor.
Open Access
- 1 September 1993
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 7 (9), 1737-1754
- https://doi.org/10.1101/gad.7.9.1737
Abstract
Nonsense mutations in a gene can accelerate the decay rate of the mRNA transcribed from that gene, a phenomenon we describe as nonsense-mediated mRNA decay. Using amber (UAG) mutants of the yeast PGK1 gene as a model system, we find that nonsense-mediated mRNA decay is position dependent, that is, nonsense mutations within the initial two-thirds of the PGK1-coding region accelerate the decay rate of the PGK1 transcript < or = 12-fold, whereas nonsense mutations within the carboxy-terminal third of the coding region have no effect on mRNA decay. Moreover, we find that this position effect reflects (1) a requirement for sequences 3' to the nonsense mutation that may be necessary for translational reinitiation or pausing, and (2) the presence of an additional sequence that, when translated, inactivates the nonsense-mediated mRNA decay pathway. This stabilizing element is positioned within the coding region such that it constitutes the boundary between nonsense mutations that do or do not affect mRNA decay. Rapid decay of PGK1 nonsense-containing transcripts is also dependent on the status of the UPF1 gene. Regardless of the position of an amber codon in the PGK1 gene, deletion of the UPF1 gene restores wild-type decay rates to nonsense-containing PGK1 transcripts.Keywords
This publication has 39 references indexed in Scilit:
- A new group of putative RNA helicasesTrends in Biochemical Sciences, 1992
- A coding region segment is necessary, but not sufficient for rapid decay of the HIS3 mRNA in yeastGene, 1992
- NAM7 nuclear gene encodes a novel member of a family of helicases with a Zn-ligand motif and is involved in mitochondrial functions in Saccharomyces cerevisiaeJournal of Molecular Biology, 1992
- Picornavirus RNA translation continues to surpriseTrends in Genetics, 1991
- ‘Omnipotent’ nonsense suppressors: new clues to an old puzzleTrends in Biochemical Sciences, 1988
- Sequences that confer β-tubulin autoregulation through modulated mRNA stability reside within exon 1 of a β-tubulin mRNACell, 1987
- Saccharomyces cerevisiae mRNA populations of different intrinsic stability in unstressed and heat shocked cells display almost constant m7GpppA:m7GpppG 5′‐cap structure ratiosFEBS Letters, 1987
- Translation is required for regulation of histone mRNA degradationCell, 1987
- Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mpl8 and pUC19 vectorsGene, 1985
- Interference of nonsense mutations with eukaryotic messenger RNA stability.Proceedings of the National Academy of Sciences of the United States of America, 1979