An unappreciated role for RNA surveillance.

Article Details


Hillman RT, Green RE, Brenner SE

An unappreciated role for RNA surveillance.

Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2.

PubMed ID
14759258 [ View in PubMed

BACKGROUND: Nonsense-mediated mRNA decay (NMD) is a eukaryotic mRNA surveillance mechanism that detects and degrades mRNAs with premature termination codons (PTC+ mRNAs). In mammals, a termination codon is recognized as premature if it lies more than about 50 nucleotides upstream of the final intron position. More than a third of reliably inferred alternative splicing events in humans have been shown to result in PTC+ mRNA isoforms. As the mechanistic details of NMD have only recently been elucidated, we hypothesized that many PTC+ isoforms may have been cloned, characterized and deposited in the public databases, even though they would be targeted for degradation in vivo. RESULTS: We analyzed the human alternative protein isoforms described in the SWISS-PROT database and found that 144 (5.8% of 2,483) isoform sequences amenable to analysis, from 107 (7.9% of 1,363) SWISS-PROT entries, derive from PTC+ mRNA. CONCLUSIONS: For several of the PTC+ isoforms we identified, existing experimental evidence can be reinterpreted and is consistent with the action of NMD to degrade the transcripts. Several genes with mRNA isoforms that we identified as PTC+--calpain-10, the CDC-like kinases (CLKs) and LARD--show how previous experimental results may be understood in light of NMD.

DrugBank Data that Cites this Article

NameUniProt ID
Gamma-aminobutyric acid type B receptor subunit 1Q9UBS5Details
Folate receptor gammaP41439Details
Sodium/potassium-transporting ATPase subunit alpha-1P05023Details
Estrogen receptor betaQ92731Details
Glutaminase kidney isoform, mitochondrialO94925Details
Potassium voltage-gated channel subfamily KQT member 2O43526Details
Atrial natriuretic peptide receptor 2P20594Details
Canalicular multispecific organic anion transporter 2O15438Details
Tissue-type plasminogen activatorP00750Details
cAMP-specific 3',5'-cyclic phosphodiesterase 4AP27815Details
Dual specificity protein kinase CLK1P49759Details
Tumor necrosis factor receptor superfamily member 10BO14763Details
Anthrax toxin receptor 1Q9H6X2Details
Microtubule-associated protein 4P27816Details
Histone deacetylase 10Q969S8Details
Cytochrome P450 3A43Q9HB55Details
Proteasome subunit alpha type-7O14818Details
Dual specificity protein kinase CLK3P49761Details
Casein kinase I isoform gamma-1Q9HCP0Details
LIM domain kinase 1P53667Details
Cyclic AMP-dependent transcription factor ATF-3P18847Details
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1P28907Details
Lymphoid enhancer-binding factor 1Q9UJU2Details
Dual specificity protein kinase CLK2P49760Details