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Lantéri, Marion; Giordanengo, Valérie; Vidal, Frédérique; Gaudray, Patrick; Lefebvre, Jean-Claude
Glycobiology (Oxford), 12/2002, Volume: 12, Issue: 12Journal Article
The synthesis of Galα1-3Gal-terminated oligosaccharides (α-Gal) epitopes has been interrupted during the course of evolution, starting with Old World primates. Partial sequences similar to the α1,3-galactosyltransferase (α1,3GalT) gene, which governs the synthesis of α-Gal epitopes, have been detected in the human genome and were found to correspond to pseudogenes. We completed the sequence of the human α1,3GalT pseudogene present on chromosome 9 and found it to be organized like the murine α1,3GalT gene. In human cell lines and several normal and tumor tissues we detected truncated transcripts corresponding to this pseudogene. Considering these mRNAs, translation of an open reading frame containing the first four translated exons but missing the two catalytic exons could predict a truncated α1,3GalT polypeptide that should be enzymatically inactive. We show that transcription of human α1,3GalT is prematurely terminated at the level of a strong transcriptional stop signal in the middle of intron VII. We were able to reproduce this effect in vitro by subcloning the implicated DNA region upstream from a reporter cDNA. The premature transcriptional arrest of human α1,3-GalT gene leads to an ectopic splicing event and to the connection of a short intronic sequence downstream from translated exons. Finally, we show that these truncated transcripts are overexpressed in cell lines with modifications of O-glycans.
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