1 research outputs found
Structural insights into nonsense-mediated mRNA decay (NMD) by electron microscopy
7 pag.; 3 figs.Nonsense-mediated mRNA decay (NMD) is a pathway that detects and degrades
mRNAs containing premature translation termination codons (PTCs). In humans,
recognition of these aberrant mRNAs requires an exon-junction-complex (EJC) placed
downstream of a PTC and the dynamic interaction of several UPF/SMG proteins, the
ribosome and the EJC. These interactions promote UPF1 phosphorylation by SMG1
kinase, triggering mRNA degradation. Recent progress in our understanding of NMD
has been achieved by combining cryo-electron microscopy, high-resolution structures,
interaction data and functional assays. These studies uncovered a mechanism regulating
SMG1 kinase as well as the architecture and functional implications of a complex
containing UPF1, UPF2, UPF3 and EJC. Collectively these findings reveal the role of
protein scaffolds and conformational changes in NMD regulation.This work was funded by the Spanish Government (SAF2011-22988 to O.L.), the ‘Red Tematica de Investigacion Cooperativa en Cancer(RTICC)’ (RD06/0020/1001 to O.L.) and the Human Frontiers Science Program (RGP39/2008 to O.L.). O.L. acknowledges also support by the‘Ramon Areces’ Foundation.Peer reviewe