The long non-coding RNA HAS2-AS1 enhances the transcription of hyaluronan synthase 2 (1005.1)

As the accumulation of the glycosaminoglycans hyaluronan (HA) into arteries wall supports cardiovascular pathologies and protein modification by attachment of beta-N-acetylglucosamine (GlcNAcylation) is involved in diabetic angiopahties, we studied the involvement of O-GlcNAcylation in the regulation of HA synthesis. Here we report that the long non coding RNA HAS2-AS1 enhances the transcription of hyaluronan synthase 2 (HAS2), the main HA synthetic enzyme in humans. We found that O-GlcNAcylation increased both HAS2 mRNA as well as HAS2-AS1 RNA, the natural antisense transcript of HAS2 ,which is complementary to exon 1 of HAS2. Such HAS2 mRNA increase could be reduced by the abrogation of HAS2-AS1. Further, we found that the HAS2-AS1 promoter was activated by O-GlcNAcylation via NF-kB, whereas HAS2 promoter did not respond to such glycosylation. The presence of HAS2 exon 1 to its promoter increased transcriptional activity after O-GlcNAcylation. As it is known that long non coding RNAs modulate epigenetic...