title: A novel function for alternative polyadenylation as a rescue pathway from NMD surveillance.
abstract: Premature termination codon (PTC) containing transcripts are subjected to a rapid degradation via nonsense-mediated decay (NMD) surveillance mechanism. By and large degradation is desired in order to prevent the translation of truncated, most likely deleterious, protein. Nevertheless, several dissimilar NMD-rescue events, capable of turning NMD-candidates into NMD-immune, are described. Yet, the extent and nature of this phenomenon is unknown. We screened the human genome for NMD-candidates transcripts. Among which we sub-grouped "pseudo-NMD" genes, which all their annotated transcripts contain PTCs, and therefore allegedly are transcribed but never translated. Here we show that alternative polyadenylation can rescue prematurely terminated transcripts, by truncating the pre-mRNA so that the PTC is now "legally" positioned. ESTs-based analysis shows that NMD-rescued genes are indeed expressed in human tissues. Furthermore, predicted NMD-rescue variants' existence is computationally verified. Hence, we suggest a novel role for the exon-truncated class of alternative polyadenylation as an NMD-rescue regulatory mechanism.
authors.affiliation: Bioinformatics Program, School of Computer Science, The Academic College of Tel Aviv-Yaffo, 4 Antokolsky St., Tel-Aviv 64044, Israel.
authors.forename: Roi
authors.initials: R
authors.lastname: Gilat
authors.forename: Dorit
authors.initials: D
authors.lastname: Shweiki
mesh_terms: D002874:Chromosome Mapping / Q000379:methods*; D018389:Codon, Nonsense / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D026723:Polyadenylation / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D014157:Transcription Factors