Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise

Mendell, Joshua T.; Sharifi, Neda; Meyers, Jennifer; Martínez-Murillo, Francisco; Dietz, Harry C.

doi:10.1038/ng1429

Cited by 761 publications

(933 citation statements)

References 30 publications

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“…NMD thus prevents production of potentially deleterious truncated proteins [39]. Second, NMD clearly serves to dampen the expression of nonfunctional transcripts arising from pseudogenes, expressed transposons, or integrated retroviruses, which frequently contain termination codons upstream of introns [40]. Finally, during programmed gene rearrangements in the T-cell receptor and immunoglobulin genes, unproductively rearranged alleles generate termination codons upstream of introns, and the resulting mRNAs are degraded by NMD [41].…”

Section: Splicing Directs Mrnp Formationmentioning

confidence: 99%

“…In addition to facilitating elimination of the nonfunctional mRNAs described above, significant evidence exists that some 3UIs serve to modulate normal gene expression [40,[43][44][45][46][47][48][49]. Three classes of 3UI-containing mRNAs are both functional and subject to NMD (Fig.…”

Section: Splicing Directs Mrnp Formationmentioning

confidence: 99%

“…If uORF translation occurs prior to translation of the main ORF, exon junctions within the main ORF are effectively in the 3 0 -UTR of the uORF, and this can elicit NMD. In this way, translation of uORFs can serve to modulate mRNA levels and thus expression of the main ORF [40]. The second class consists of mRNAs in which a termination codon upstream of an exon junction is ''intentionally'' introduced by alternative splicing.…”

Section: Splicing Directs Mrnp Formationmentioning

confidence: 99%

“…As a result, hundreds of transcripts that would otherwise be subject to NMD are up-regulated, and most of these encode proteins important for neural function [46]. 3UI-containing transcripts are also enriched for mRNAs involved in amino acid metabolism, starvation, ER stress, and hypoxia [40,47,49]. These enrichments led to the discovery that NMD is inhibited during stress through a mechanism involving phosphorylation of translation initiation factor, eIF2a.…”

Section: A a Bicknell Et Almentioning

confidence: 99%

See 3 more Smart Citations

Introns in UTRs: Why we should stop ignoring them

et al. 2012

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Although introns in 5 0 -and 3 0 -untranslated regions (UTRs) are found in many protein coding genes, rarely are they considered distinctive entities with specific functions. Indeed, mammalian transcripts with 3 0 -UTR introns are often assumed nonfunctional because they are subject to elimination by nonsense-mediated decay (NMD). Nonetheless, recent findings indicate that 5 0 -and 3 0 -UTR intron status is of significant functional consequence for the regulation of mammalian genes. Therefore these features should be ignored no longer.

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Section: Splicing Directs Mrnp Formationmentioning

confidence: 99%

Section: Splicing Directs Mrnp Formationmentioning

confidence: 99%

Section: Splicing Directs Mrnp Formationmentioning

confidence: 99%

Section: A a Bicknell Et Almentioning

confidence: 99%

See 2 more Smart Citations

Introns in UTRs: Why we should stop ignoring them

et al. 2012

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“…[8][9][10] In addition to its role in quality control, NMD also regulates gene expression of so-called natural substrates of NMD. [11][12][13][14][15] Proteins that have a central role in NMD, such as UPF1, UPF2, UPF3/UPF3a and UPF3X/UPF3b are highly conserved from yeast to human. The requirement for these UPF proteins in NMD is illustrated by the fact that the downregulation of any one of them results in an inhibition of NMD.…”

mentioning

confidence: 99%

Caspases shutdown nonsense-mediated mRNA decay during apoptosis

et al. 2015

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Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance mechanism that plays integral roles in eliminating mRNAs with premature termination codons to prevent the synthesis of truncated proteins that could be pathogenic. One response to the accumulation of detrimental proteins is apoptosis, which involves the activation of enzymatic pathways leading to protein and nucleic acid cleavage and culminating in cell death. It is not clear whether NMD is required to ensure the accurate expression of apoptosis genes or is no longer necessary since cytotoxic proteins are not an issue during cell death. The present study shows that caspases cleave the two NMD factors UPF1 and UPF2 during apoptosis impairing NMD. Our results demonstrate a new regulatory pathway for NMD that occurs during apoptosis and provide evidence for role of the UPF cleaved fragments in apoptosis and NMD inhibition.

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Nonsense‐mediated mRNA decay of the ferric and cupric reductase mRNAs FRE1 and FRE2 in Saccharomyces cerevisiae

2019

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The nonsense‐mediated mRNA decay (NMD) pathway regulates mRNAs that aberrantly terminate translation. This includes aberrant mRNAs and functional natural mRNAs. Natural mRNA degradation by NMD is triggered by mRNA features and environmental cues. Saccharomyces cerevisiae encodes multiple proteins with ferric and cupric reductase activity. Here, we examined the regulation by NMD of two mRNAs, FRE1 and FRE2, encoding ferric and cupric reductases in S. cerevisiae. We found that FRE2 mRNAs are regulated by NMD under noninducing conditions and that the FRE2 3′‐UTR contributes to the degradation of the mRNAs by NMD. Conversely, FRE1 mRNAs are not regulated by NMD under comparable conditions. These findings suggest that regulation of functionally related mRNAs by NMD can be differential and conditional.

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Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise

Cited by 761 publications

References 30 publications

Introns in UTRs: Why we should stop ignoring them

Introns in UTRs: Why we should stop ignoring them

Caspases shutdown nonsense-mediated mRNA decay during apoptosis

Nonsense‐mediated mRNA decay of the ferric and cupric reductase mRNAs FRE1 and FRE2 in Saccharomyces cerevisiae

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