Nonsense-mediated mRNA Decay in Saccharomyces cerevisiae: A Quality Control Mechanism That Degrades Transcripts Harboring Premature Termination Codons

2001 ◽  
Vol 66 (0) ◽  
pp. 321-328 ◽  
Author(s):  
C.I. GONZALEZ ◽  
W. WANG ◽  
S.W. PELTZ
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Quality Control ◽  
Mrna Decay ◽  
Premature Termination ◽  
Control Mechanism ◽  
Premature Termination Codons ◽  
Nonsense Mediated Mrna Decay ◽  
Quality Control Mechanism

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.

scholarly journals Inhibition of nonsense-mediated mRNA decay (NMD) by a new chemical molecule reveals the dynamic of NMD factors in P-bodies

2007 ◽  
Vol 178 (7) ◽  
pp. 1145-1160 ◽  
Author(s):  
Sébastien Durand ◽  
Nicolas Cougot ◽  
Florence Mahuteau-Betzer ◽  
Chi-Hung Nguyen ◽  
David S. Grierson ◽  
...  
Keyword(s):  
Quality Control ◽  
Mrna Decay ◽  
Control Mechanism ◽  
Premature Termination Codon ◽  
Processing Bodies ◽  
P Bodies ◽  
Molecule Inhibitor ◽  
Nonsense Mediated Mrna Decay ◽  
Quality Control Mechanism ◽  
Insight Into

In mammals, nonsense-mediated mRNA decay (NMD) is a quality-control mechanism that degrades mRNA harboring a premature termination codon to prevent the synthesis of truncated proteins. To gain insight into the NMD mechanism, we identified NMD inhibitor 1 (NMDI 1) as a small molecule inhibitor of the NMD pathway. We characterized the mode of action of this compound and demonstrated that it acts upstream of hUPF1. NMDI 1 induced the loss of interactions between hSMG5 and hUPF1 and the stabilization of hyperphosphorylated isoforms of hUPF1. Incubation of cells with NMDI 1 allowed us to demonstrate that NMD factors and mRNAs subject to NMD transit through processing bodies (P-bodies), as is the case in yeast. The results suggest a model in which mRNA and NMD factors are sequentially recruited to P-bodies.

scholarly journals Mechanisms and Regulation of Nonsense-Mediated mRNA Decay and Nonsense-Associated Altered Splicing in Lymphoid Cells

2020 ◽  
Author(s):  
Jean-Marie Lambert ◽  
Mohamad Omar Ashi ◽  
Nivine Srour ◽  
Laurent Delpy ◽  
Jérôme Saulière
Keyword(s):  
Quality Control ◽  
Mrna Decay ◽  
Dominant Negative ◽  
Lymphoid Cells ◽  
Surveillance Systems ◽  
Rna Surveillance ◽  
Accelerated Degradation ◽  
Premature Termination Codons ◽  
Rna Quality Control ◽  
Nonsense Mediated Mrna Decay

The presence of premature termination codons (PTCs) in transcripts is dangerous for the cell as they encode potentially deleterious truncated proteins that can act with dominant-negative or gain-of-function effects. To avoid synthesis of these shortened polypeptides, several RNA surveillance systems can be activated to decrease the level of PTC-containing mRNAs. Nonsense-mediated mRNA decay (NMD) ensures an accelerated degradation of mRNAs harboring PTCs by using several key NMD factors such as up-frameshift (UPF) proteins. Another pathway called nonsense-associated altered splicing (NAS) upregulates transcripts that have skipped disturbing PTCs by alternative splicing. Therefore, these RNA quality control processes eliminate abnormal PTC-containing mRNAs from the cells by using positive and negative responses. In this review, we will describe the general mechanisms of NMD and NAS and their respective involvement in the decay of aberrant immunoglobulin and TCR transcripts in lymphoid cells.

scholarly journals Premature termination codons in SOD1 causing Amyotrophic Lateral Sclerosis are predicted to escape the nonsense-mediated mRNA decay

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Claire Guissart ◽  
Kevin Mouzat ◽  
Jovana Kantar ◽  
Baptiste Louveau ◽  
Paul Vilquin ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mrna Decay ◽  
Premature Termination ◽  
Underlying Mechanism ◽  
Missense Mutations ◽  
Gene Encoding ◽  
Premature Termination Codons ◽  
Nonsense Mediated Mrna Decay ◽  
Inherited Mutations ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is the most common and severe adult-onset motoneuron disease and has currently no effective therapy. Approximately 20% of familial ALS cases are caused by dominantly-inherited mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1), which represents one of the most frequent genetic cause of ALS. Despite the overwhelming majority of ALS-causing missense mutations in SOD1, a minority of premature termination codons (PTCs) have been identified. mRNA harboring PTCs are known to be rapidly degraded by nonsense-mediated mRNA decay (NMD), which limits the production of truncated proteins. The rules of NMD surveillance varying with PTC location in mRNA, we analyzed the localization of PTCs in SOD1 mRNA to evaluate whether or not those PTCs can be triggered to degradation by the NMD pathway. Our study shows that all pathogenic PTCs described in SOD1 so far can theoretically escape the NMD, resulting in the production of truncated protein. This finding supports the hypothesis that haploinsufficiency is not an underlying mechanism of SOD1 mutant-associated ALS and suggests that PTCs found in the regions that trigger NMD are not pathogenic. Such a consideration is particularly important since the availability of SOD1 antisense strategies, in view of variant treatment assignment.

scholarly journals Mechanisms and Regulation of Nonsense-Mediated mRNA Decay and Nonsense-Associated Altered Splicing in Lymphocytes

2020 ◽  
Vol 21 (4) ◽  
pp. 1335 ◽  
Author(s):  
Jean-Marie Lambert ◽  
Mohamad Omar Ashi ◽  
Nivine Srour ◽  
Laurent Delpy ◽  
Jérôme Saulière
Keyword(s):  
Quality Control ◽  
Alternative Splicing ◽  
Mrna Decay ◽  
Dominant Negative ◽  
Surveillance Systems ◽  
Rna Surveillance ◽  
Accelerated Degradation ◽  
Premature Termination Codons ◽  
Rna Quality Control ◽  
Nonsense Mediated Mrna Decay

The presence of premature termination codons (PTCs) in transcripts is dangerous for the cell as they encode potentially deleterious truncated proteins that can act with dominant-negative or gain-of-function effects. To avoid the synthesis of these shortened polypeptides, several RNA surveillance systems can be activated to decrease the level of PTC-containing mRNAs. Nonsense-mediated mRNA decay (NMD) ensures an accelerated degradation of mRNAs harboring PTCs by using several key NMD factors such as up-frameshift (UPF) proteins. Another pathway called nonsense-associated altered splicing (NAS) upregulates transcripts that have skipped disturbing PTCs by alternative splicing. Thus, these RNA quality control processes eliminate abnormal PTC-containing mRNAs from the cells by using positive and negative responses. In this review, we describe the general mechanisms of NMD and NAS and their respective involvement in the decay of aberrant immunoglobulin and TCR transcripts in lymphocytes.

scholarly journals Premature termination codons in PRPF31 cause retinitis pigmentosa via haploinsufficiency due to nonsense-mediated mRNA decay

2008 ◽  
Vol 118 (4) ◽  
pp. 1519-1531 ◽  
Author(s):  
Thomas Rio Frio ◽  
Nicholas M. Wade ◽  
Adriana Ransijn ◽  
Eliot L. Berson ◽  
Jacques S. Beckmann ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Mrna Decay ◽  
Premature Termination ◽  
Premature Termination Codons ◽  
Nonsense Mediated Mrna Decay

scholarly journals Mitophagy as a quality control mechanism in Saccharomyces cerevisiae

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Hagai Abeliovich ◽  
Mostafa Zarei ◽  
Kristoffer T.G. Rigbolt ◽  
Richard J. Youle ◽  
Joern Dengjel
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Quality Control ◽  
Control Mechanism ◽  
Quality Control Mechanism
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