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 cornputationally verified. Hence, we suggest a novel role for the exon-truncated class of alternative polyadenylation as an NMD-rescue regulatory mechanism. (c) 2006 Elsevier Inc. All rights reserved.