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Splicing and 3′ end formation in the definition of nonsense‐mediated decay‐competent human β‐globin mRNPs
Author(s) -
NeuYilik Gabriele,
Gehring Niels H.,
Thermann Rolf,
Frede Ute,
Hentze Matthias W.,
Kulozik Andreas E.
Publication year - 2001
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/20.3.532
Subject(s) - biology , nonsense , nonsense mediated decay , beta (programming language) , rna splicing , globin , genetics , microbiology and biotechnology , gene , rna , computer science , programming language
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 mRNPs 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 mRNP particles critically depends on splicing but does not require the presence of a poly(A) tail.