scholarly journals Nonsense-Mediated mRNA Decay, a Finely Regulated Mechanism

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 141
Author(s):  
Fabrice Lejeune
Keyword(s):  
Mrna Decay ◽  
Premature Termination ◽  
Premature Termination Codon ◽  
Human Cells ◽  
Termination Codon ◽  
Physiological Conditions ◽  
Expression Of Genes ◽  
Nonsense Mediated Mrna Decay ◽  
Different Levels

Nonsense-mediated mRNA decay (NMD) is both a mechanism for rapidly eliminating mRNAs carrying a premature termination codon and a pathway that regulates many genes. This implies that NMD must be subject to regulation in order to allow, under certain physiological conditions, the expression of genes that are normally repressed by NMD. Therapeutically, it might be interesting to express certain NMD-repressed genes or to allow the synthesis of functional truncated proteins. Developing such approaches will require a good understanding of NMD regulation. This review describes the different levels of this regulation in human cells.

scholarly journals Transcriptome analysis of alternative splicing-coupled nonsense-mediated mRNA decay in human cells reveals broad regulatory potential

2020 ◽  
Author(s):  
Courtney E. French ◽  
Gang Wei ◽  
James P. B. Lloyd ◽  
Zhiqiang Hu ◽  
Angela N. Brooks ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Rna Splicing ◽  
Mrna Decay ◽  
Premature Termination ◽  
Strong Predictor ◽  
Premature Termination Codon ◽  
Human Cells ◽  
Termination Codon ◽  
Nonsense Mediated Mrna Decay ◽  
Regulatory Potential

AbstractTo explore the regulatory potential of nonsense-mediated mRNA decay (NMD) coupled with alternative splicing, we globally surveyed the transcripts targeted by this pathway via RNA-Seq analysis of HeLa cells in which NMD had been inhibited. We identified putative NMD-targeted transcripts as those with a termination codon more than 50 nucleotides upstream of an exon-exon junction (premature termination as defined by the ‘50nt rule’) and that significantly increased in abundance upon NMD inhibition. We additionally controlled for potential transcriptional up-regulation by requiring the putative NMD targets to increase in abundance substantially more than the isoforms from the same gene that do not contain a premature termination codon. This resulted in a conservative set of 2,793 transcripts derived from 2,116 genes as physiological NMD targets (9.2% of expressed transcripts and >20% of alternatively spliced genes). Our analysis identified previously inferred unproductive isoforms and numerous heretofore-uncharacterized ones. NMD-targeted transcripts were derived from genes involved in many functional categories, and are particularly enriched for RNA splicing genes as well as for those harboring ultraconserved elements. By investigating the features of all transcripts impacted by NMD, we find that the 50nt rule is a strong predictor of NMD degradation while 3’ UTR length on its own generally has only a small effect in this human cell line. Additionally, thousands more transcripts without a premature termination codon in the main coding sequence contain a uORF and display significantly increased abundance upon NMD inhibition indicating potentially widespread regulation through decay coupled with uORF translation. Our results support that alternative splicing coupled with NMD is a prevalent post-transcriptional mechanism in human cells with broad potential for biological regulation.

scholarly journals Nonsense-Mediated mRNA Decay Mutation in Aspergillus nidulans

2006 ◽  
Vol 5 (11) ◽  
pp. 1838-1846 ◽  
Author(s):  
Igor Y. Morozov ◽  
Susana Negrete-Urtasun ◽  
Joan Tilburn ◽  
Christine A. Jansen ◽  
Mark X. Caddick ◽  
...  
Keyword(s):  
Aspergillus Nidulans ◽  
Mrna Decay ◽  
Premature Termination ◽  
Regulation Of Gene Expression ◽  
Premature Termination Codon ◽  
Termination Codon ◽  
Urate Oxidase ◽  
Genes Encoding ◽  
Nonsense Mediated Mrna Decay ◽  
Nonsense Codons

ABSTRACT An Aspergillus nidulans mutation, designated nmdA1, has been selected as a partial suppressor of a frameshift mutation and shown to truncate the homologue of the Saccharomyces cerevisiae nonsense-mediated mRNA decay (NMD) surveillance component Nmd2p/Upf2p. nmdA1 elevates steady-state levels of premature termination codon-containing transcripts, as demonstrated using mutations in genes encoding xanthine dehydrogenase (hxA), urate oxidase (uaZ), the transcription factor mediating regulation of gene expression by ambient pH (pacC), and a protease involved in pH signal transduction (palB). nmdA1 can also stabilize pre-mRNA (unspliced) and wild-type transcripts of certain genes. Certain premature termination codon-containing transcripts which escape NMD are relatively stable, a feature more in common with certain nonsense codon-containing mammalian transcripts than with those in S. cerevisiae. As in S. cerevisiae, 5′ nonsense codons are more effective at triggering NMD than 3′ nonsense codons. Unlike the mammalian situation but in common with S. cerevisiae and other lower eukaryotes, A. nidulans is apparently impervious to the position of premature termination codons with respect to the 3′ exon-exon junction.

scholarly journals Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay

RNA ◽  
2008 ◽  
Vol 14 (3) ◽  
pp. 563-576 ◽  
Author(s):  
A. L. Silva ◽  
P. Ribeiro ◽  
A. Inacio ◽  
S. A. Liebhaber ◽  
L. Romao
Keyword(s):  
Mrna Decay ◽  
Premature Termination ◽  
Binding Protein ◽  
Premature Termination Codon ◽  
Termination Codon ◽  
Nonsense Mediated Mrna Decay

Aberrant termination triggers nonsense-mediated mRNA decay

2006 ◽  
Vol 34 (1) ◽  
pp. 39-42 ◽  
Author(s):  
N. Amrani ◽  
S. Dong ◽  
F. He ◽  
R. Ganesan ◽  
S. Ghosh ◽  
...  
Keyword(s):  
Quality Control ◽  
Untranslated Region ◽  
Mrna Decay ◽  
Premature Termination ◽  
Control Mechanism ◽  
Premature Termination Codon ◽  
Release Factor ◽  
Mrna Decapping ◽  
Nonsense Mediated Mrna Decay ◽  
Quality Control Mechanism

NMD (nonsense-mediated mRNA decay) is a cellular quality-control mechanism in which an otherwise stable mRNA is destabilized by the presence of a premature termination codon. We have defined the set of endogenous NMD substrates, demonstrated that they are available for NMD at every round of translation, and showed that premature termination and normal termination are not equivalent biochemical events. Premature termination is aberrant, and its NMD-stimulating defects can be reversed by the presence of tethered poly(A)-binding protein (Pab1p) or tethered eRF3 (eukaryotic release factor 3) (Sup35p). Thus NMD appears to be triggered by a ribosome's failure to terminate adjacent to a properly configured 3′-UTR (untranslated region), an event that may promote binding of the UPF/NMD factors to stimulate mRNA decapping.

Sign in / Sign up

Export Citation Format

Share Document