Regulatory RNAs of the Transglutaminase 2 gene interfere with its expression in leukaemic cell lines after ATRA treatment

TGM2 is a long gene modulated by ATRA, which generates truncated variants by RNApol II pausing at checkpoints through alternative splicing and polyadenylation, along with two non-coding RNAs. One is a lncRNA transcribed from the first intron, while the other RNA, designed as LEV (Last Exons Variant), starts from intron 10 and contains the last 3 exons including the 3’UTR of the gene. The structure of the lncRNA suggests its multifunctional role, while LEV mimics exactly the last portion of the full-length TG2 transcript. RNA immunoprecipitation experiments and the use of antisense oligonucleotides demonstrate that lncRNA binds RNApol II interfering with the expression of full-length TG2 and LEV, while LEV appears associated to modulation of the altered TGH levels in mechanisms dependent on the involvement of the transcriptional factor GATA3. The functional significance of these findings will be discussed in relation with the presence of altered enzyme isoforms.