Where does nonsense-mediated decay occur?
One of the best-studied RNA surveillance pathways is the Nonsense-mediated decay (NMD) pathway, which targets mRNAs harboring premature termination codons (PTC) for degradation. This mechanism operates in the cytoplasm and is intimately linked to translation termination (2,3).
What activates nonsense-mediated decay?
Nonsense-mediated RNA decay (NMD) is an mRNA surveillance mechanism which rapidly degrades select cytoplasmic mRNAs. We and others have shown that NMD is a dynamically regulated process inhibited by amino acid deprivation, hypoxia, and other cellular stresses commonly generated by the tumor microenvironment.
What is nonsense-mediated mRNA decay what is its significance in the cell?
Nonsense-mediated mRNA decay (NMD) is an mRNA quality-control mechanism that typifies all eukaryotes examined to date. NMD surveys newly synthesized mRNAs and degrades those that harbor a premature termination codon (PTC), thereby preventing the production of truncated proteins that could result in disease in humans.
What is the NMD pathway?
Nonsense-mediated RNA decay (NMD) was originally discovered as a cellular surveillance pathway that safeguards the quality of mRNA transcripts in eukaryotic cells. In its canonical function, NMD prevents translation of mutant mRNAs harboring premature termination codons (PTCs) by targeting them for degradation.
What is nonstop mediated decay?
Nonstop decay is a second translational surveillance pathway in which cells repress the activity of mRNAs lacking stop codons through both mRNA and protein decay mechanisms (Frischmeyer et al., 2002; Bengtson and Joazeiro, 2010).
What is Nmd_transcript_variant?
A variant in a transcript that is the target of nonsense-mediated mRNA decay. non coding transcript variant + partially duplicated transcript + splicing variant +
Does NMD occur in nucleus?
Our data indicate that there is no discernible nuclear NMD in yeast, based on biochemical as well as FISH assays. Our results also indicate that NMD is fully functional during heat shock. It has previously been shown that mammalian NMD does not occur during heat shock on an HSP70 gene.
Why is translational regulation important?
Translational control governs the efficiency of mRNAs and thus plays an important role in modulating the expression of many genes that respond to endogenous or exogenous signals such as nutrient supply, hormones, or stress.
What is premature termination codon?
Premature termination codons (PTCs) arise from single nucleotide mutations that convert a canonical triplet nucleotide codon into one of three stop codons, e.g., TAG, TGA, or TAA. PTCs are often more deleterious than missense mutations because they result in the loss of protein expression.
How is mRNA turnover regulated?
Instead, mRNA turnover is a complex set of cellular processes regulated by mechanisms independent from transcription. Once transcribed, mRNAs associate with a host of protein factors throughout their lifetimes, some of which are stably bound while others are subject to dynamic exchange.
What is a cryptic splice site?
Cryptic splice sites also match the consensus motifs, and by definition they are splice sites that are not detectably used in wild-type pre-mRNA, but are only selected as a result of a mutation elsewhere in the gene, most often at the authentic splice site.