Novel insights into human RNA polymerase III transcription: non canonical termination and biogenesis of potential regulatory RNAs

Transcription by human RNA polymerase III has been studied extensively to date, but many processes still need to be fully elucidated to get a more comprehensive picture. Here, we redefined the minimal sequence requirements for human RNA polymerase III termination and we investigated a novel kind of post-transcriptional gene silencing carried out by antisense AluRNAs derived from the 3'-UTR of human mRNAs. Starting from the observation that ? ¼ of human tRNA genes are enriched in canonical terminators located at ?50 bp from the 3'-end of the tRNA coding sequence, we identified several novel non canonical terminators located further upstream at which RNA polymerase III terminates with different efficiencies, generally lower than those observed for termination at the canonical ?T4 sites. Considering that more than one million of type 2 promoter elements are scattered through the human genome (tDNAs, Alu, MIR, etc), read-through at non-canonical sites could end up in the biogenesis of primary RNAs, with potential regulatory functions as previously observed for RNA polymerase III-derived miRNA, embedded in the 3'trailer of predicted type 2 promoter transcripts. Relaxed RNA polymerase III terminators could thus represent the evolution of a more sophisticated regulatory mechanism for the biogenesis of small RNAs. Additionally, we found that an antisense AluY RNA, transcribed from the 3'UTR of TERF2 mRNA is likely to trigger the silencing of its cognate mRNA by targeting its complementary sequence and speculated that the target specificity resides in its unique 3'trailer.