Longevity regulation by NMD-mediated mRNA quality control

Longevity regulation by NMD-mediated mRNA quality control

Proper maintenance of biological components is crucial for longevity and healthy aging. Although the role of homeostatic maintenance systems for DNA and protein in longevity is established, it remains largely unknown for RNA. In our recent work, we show that nonsense-mediated mRNA decay (NMD) promotes longevity in the roundworm C. elegans by enhancing RNA quality control. We find that the activ...

CYP3A5 mRNA degradation by nonsense mediated mRNA decay (NMD)

The uORF-containing thrombopoietin mRNA escapes nonsense-mediated decay (NMD)

Platelet production is induced by the cytokine thrombopoietin (TPO). It is physiologically critical that TPO expression is tightly regulated, because lack of TPO causes life-threatening thrombocytopenia while an excess of TPO results in thrombocytosis. The plasma concentration of TPO is controlled by a negative feedback loop involving receptor-mediated uptake of TPO by platelets. Furthermore, T...

Structural insights into nonsense-mediated mRNA decay (NMD) by electron microscopy.

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 kina...

Regulation of mRNA translation as a conserved mechanism of longevity control.

Appropriate regulation of mRNA translation is essential for growth and survival and the pathways that regulate mRNA translation have been highly conserved throughout eukaryotic evolution. Translation is controlled by a complex set of mechanisms acting at multiple levels, ranging from global protein synthesis to individual mRNAs. Recently, several mutations that perturb regulation of mRNA transl...