Nonsense-mediated decay approaches the clinic.

Abstract

Nonsense-mediated decay (NMD) eliminates mRNAs containing premature termination codons and thus helps limit the synthesis of abnormal proteins. New results uncover a broader role of NMD as a pathway that also affects the expression of wild-type genes and alternative-splice products. Because the mechanisms by which NMD operates have received much attention, we discuss here the emerging awareness of the impact of NMD on the manifestation of human genetic diseases. We explore how an understanding of NMD accounts for phenotypic differences in diseases caused by premature termination codons. Specifically, we consider how the protective function of NMD sometimes benefits heterozygous carriers and, in contrast, sometimes contributes to a clinical picture of protein deficiency by inhibiting expression of partially functional proteins. Potential 'NMD therapeutics' will therefore need to strike a balance between the general physiological benefits of NMD and its detrimental effects in cases of specific genetic mutations.

• Authors: Jill A Holbrook, Gabriele Neu-Yilik, Matthias W Hentze, Andreas E Kulozik
• Journal: Nature genetics (Nat Genet) Vol. 36 Issue 8 Pg. 801-8 (Aug 2004) ISSN: 1061-4036 [Print] United States
• PMID: 15284851 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Codon, Nonsense
• RNA, Messenger

Topics

• Alternative Splicing
• Codon, Nonsense
• Gene Expression Regulation
• Genes, Tumor Suppressor
• Genetic Diseases, Inborn (genetics, therapy)
• Humans
• Models, Genetic
• RNA, Messenger