An unappreciated role for RNA surveillance.
Article Details
- CitationCopy to clipboard
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]
- Abstract
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
- Polypeptides
Name UniProt ID Gamma-aminobutyric acid type B receptor subunit 1 Q9UBS5 Details Folate receptor gamma P41439 Details Sodium/potassium-transporting ATPase subunit alpha-1 P05023 Details Estrogen receptor beta Q92731 Details Formimidoyltransferase-cyclodeaminase O95954 Details Glutaminase kidney isoform, mitochondrial O94925 Details Potassium voltage-gated channel subfamily KQT member 2 O43526 Details Atrial natriuretic peptide receptor 2 P20594 Details Canalicular multispecific organic anion transporter 2 O15438 Details Tissue-type plasminogen activator P00750 Details cAMP-specific 3',5'-cyclic phosphodiesterase 4A P27815 Details Dual specificity protein kinase CLK1 P49759 Details Tumor necrosis factor receptor superfamily member 10B O14763 Details Anthrax toxin receptor 1 Q9H6X2 Details Caspase-8 Q14790 Details Microtubule-associated protein 4 P27816 Details Histone deacetylase 10 Q969S8 Details Cytochrome P450 3A43 Q9HB55 Details Proteasome subunit alpha type-7 O14818 Details Dual specificity protein kinase CLK3 P49761 Details Casein kinase I isoform gamma-1 Q9HCP0 Details LIM domain kinase 1 P53667 Details Cyclic AMP-dependent transcription factor ATF-3 P18847 Details ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 P28907 Details Lymphoid enhancer-binding factor 1 Q9UJU2 Details Dual specificity protein kinase CLK2 P49760 Details