Email updates

Keep up to date with the latest news and content from Genome Biology and BioMed Central.

Open Access Highly Accessed Research

An unappreciated role for RNA surveillance

R Tyler Hillman12, Richard E Green23 and Steven E Brenner123*

Author Affiliations

1 Department of Bioengineering, University of California, Berkeley, CA 94720-3102, USA

2 Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720-3102, USA

3 Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3102, USA

For all author emails, please log on.

Genome Biology 2004, 5:R8  doi:10.1186/gb-2004-5-2-r8

Published: 2 February 2004

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.