NMD: Nonsense-Mediated Defense

Autism and Nonsense Mediated Decay (NMD)

In 2010 large scale screening study of a number of families with neurodevelopmental disorders including autism, a family from Belgium with two brothers and one brother was presented with ID and autism; it was found that he has a single nucleotide substitution in UPF3b 1103G>A forming Arg368Gln (R368Q). The mother of the boy was found to be a carrier too. Interestingly, the missense mutation in ...

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...

Perturbation of thymocyte development in nonsense-mediated decay (NMD)-deficient mice.

The random nature of T-cell receptor-β (TCR-β) recombination needed to generate immunological diversity dictates that two-thirds of alleles will be out-of-frame. Transcripts derived from nonproductive rearrangements are cleared by the nonsense-mediated mRNA decay (NMD) pathway, the process by which cells selectively degrade transcripts harboring premature termination codons. Here, we demonstrat...

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...