Open AccessJournal Article
Evidence for degradation of mRNA encoding alpha-L-iduronidase in Hurler fibroblasts with premature termination alleles.
K P Menon,E F Neufeld +1 more
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TLDR
RT-PCR showed a normal level of a segment covering exons 1 and 2 in Hurler cells homozygous for alleles bearing the nonsense mutations, Q70X or W402X, indicating that the nonsense RNA was degraded to fragment(s), independent of the position of the mutation.Abstract:
Mutations in the gene encoding alpha-L-iduronidase (IDUA) are the cause of Hurler syndrome. Fibroblasts from patients homozygous for nonsense IDUA alleles have much reduced mRNA detectable by Northern analysis, as has been observed in many other instances of premature translation termination. Yet RT-PCR (reverse transcription followed by PCR amplification) showed a normal level of a segment covering exons 1 and 2 in Hurler cells homozygous for alleles bearing the nonsense mutations, Q70X or W402X. The 3' end of the segment was between exons 2 and 4. The results indicate that the nonsense RNA was degraded to fragment(s), independent of the position of the mutation (exon 2 or exon 9, respectively). Treatment of the cells with cycloheximide resulted in some increase of intact mRNA, suggesting that translation is required for mRNA degradation.read more
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At Least One Intron Is Required for the Nonsense-Mediated Decay of Triosephosphate Isomerase mRNA: a Possible Link between Nuclear Splicing and Cytoplasmic Translation
TL;DR: The results demonstrate that TPI intron 6 functions to position the boundary because it is the 3′-most intron, and the proposed scanning complex may have a greater unwinding capability than the complex that scans for a translation initiation codon.
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Inherited Mutations in PTEN That Are Associated with Breast Cancer, Cowden Disease, and Juvenile Polyposis
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Lori Friedman,Csilla Szabo,Elizabeth A. Ostermeyer,Patrick Dowd,Lesley M. Butler,Tari Park,Ming K. Lee,Ellen L. Goode,Sarah Rowell,Mary Claire King +9 more
TL;DR: Thirty-seven families with four or more cases of breast cancer or breast and ovarian cancer were analyzed for mutations in BRCA1, and five families of Ashkenazi Jewish descent carried the 185delAG mutation and shared the same haplotype at eight polymorphic markers spanning approximately 850 kb at B RCA1.
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A mutated human homologue to yeast Upf1 protein has a dominant-negative effect on the decay of nonsense-containing mRNAs in mammalian cells.
TL;DR: It is demonstrated that expression of human Upf1 protein harboring an arginine-to-cysteine mutation at residue 844 within the RNA helicase domain acts in a dominant-negative fashion to abrogate the decay of nonsense-containing mRNA that takes place in association with nuclei or in the cytoplasm.
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