Nonsense-mediated mRNA decay - mechanisms of substrate mRNA recognition and degradation in mammalian cells
| Autor: | Christoph Schweingruber, Oliver Mühlemann, Simone C. Rufener, David Zünd, Akio Yamashita |
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| Rok vydání: | 2012 |
| Předmět: |
RNA Stability
Nonsense-mediated decay Biophysics Biology Biochemistry 03 medical and health sciences Exon Structural Biology P-bodies Genetics Protein biosynthesis Animals Phosphorylation Molecular Biology 3' Untranslated Regions 030304 developmental biology Regulation of gene expression Mammals 0303 health sciences Messenger RNA Three prime untranslated region 030302 biochemistry & molecular biology Peptide Chain Termination Translational Cell biology Nonsense Mediated mRNA Decay Open reading frame Ribonucleoproteins Protein Biosynthesis Trans-Activators RNA Helicases |
| Zdroj: | Europe PubMed Central Biochimica et biophysica acta |
| ISSN: | 0006-3002 |
| Popis: | The nonsense-mediated mRNA decay (NMD) pathway is well known as a translation-coupled quality control system that recognizes and degrades aberrant mRNAs with truncated open reading frames (ORF) due to the presence of a premature termination codon (PTC). However, a more general role of NMD in posttranscriptional regulation of gene expression is indicated by transcriptome-wide mRNA profilings that identified a plethora of physiological mRNAs as NMD targets. In this review, we focus on mechanistic aspects of target mRNA identification and degradation in mammalian cells, based on the available biochemical and genetic data, and point out knowledge gaps. Translation termination in a messenger ribonucleoprotein particle (mRNP) environment lacking necessary factors for proper translation termination emerges as a key determinant for subjecting an mRNA to NMD, and we therefore review recent structural and mechanistic insight into translation termination. In addition, the central role of UPF1, its crucial phosphorylation/dephosphorylation cycle and dynamic interactions with other NMD factors are discussed. Moreover, we address the role of exon junction complexes (EJCs) in NMD and summarize the functions of SMG5, SMG6 and SMG7 in promoting mRNA decay through different routes. This article is part of a Special Issue entitled: RNA Decay mechanisms. |
| Databáze: | OpenAIRE |
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