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- Title
Splicing and 3' end formation in the definition of nonsense-mediated decay-competent human ß-globin mRNPs.
- Authors
Neu-Yilik, Gabriele; Gehring, Niels H.; Thermann, Rolf; Frede, Ute; Hentze, Matthias W.; Kulozik, Andreas E.
- Abstract
Premature translation termination codons are common causes of genetic disorders. mRNAs with such mutations are degraded by a surveillance mechanism termed nonsense-mediated decay (NMD), which represents a phylogenetically widely conserved post-transcriptional mechanism for the quality control of gene expression. How NMD-competent mRNAs are formed and specified remains a central question. Here, we have used human β-globin mRNA as a model system to address the role of splicing and polyadenylation for human NMD. We show that (i) splicing is an indispensable component of the human β-globin NMD pathway, which cannot be compensated for by exonic β-globin 'failsafe' sequences; (ii) the spatial requirements of human β-globin NMD, as signified by the maximal distance of the nonsense mutation to the final exon-exon junction, are less constrained than in yeast; and (iii) non-polyadenylated mRNAs with a histone 3' end are NMD competent. Thus, the formation of NMD-competent mRNA particles critically depends on splicing but does not require the presence of a poly(A) tail.
- Subjects
GENETIC regulation; RNA splicing; HISTONES; MESSENGER RNA; GENE expression; GENETIC transcription
- Publication
EMBO Journal, 2001, Vol 20, Issue 3, p532
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/20.3.532