Details

Autor(en) / Beteiligte

• Schweingruber, Christoph
• Rufener, Simone C.
• Zünd, David
• Yamashita, Akio
• Mühlemann, Oliver

Titel

Nonsense-mediated mRNA decay — Mechanisms of substrate mRNA recognition and degradation in mammalian cells

Ist Teil von

• Biochimica et biophysica acta, 2013-06, Vol.1829 (6-7), p.612-623

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. ► Translation termination distant from PABP triggers NMD. ► EJCs are enhancers of NMD and differentially deposited onto spliced mRNA. ► UPF1 ATPase and RNA helicase is tightly regulated ► Phosphorylation of UPF1 is crucial for NMD but appears to not affect UPF1 ATPase/helicase activities. ► SMG5, SMG6, SMG7 and PNRC2 appear to promote mRNA decay through different routes.