Final Report Summary - EPINCRNA (Epigenetic and genome stability: non coding RNA-mediated chromatin modifications in S. cerevisiae)
The vast majority of the eukaryotes genome is non-protein coding raising the question of the role of the dark matter of the genome. It is now admitted that pervasive transcription generates thousands of noncoding transcripts that regulate gene expression and have broad impacts on development and disease. Among the long non coding (lnc)RNAs, antisense transcripts have been poorly studied despite their putative regulatory importance. Several functional examples include X-chromosome inactivation, maintenance of pluripotency and transcriptional regulation. RNA interference pathways are absent in the budding yeast but works from our laboratory and others showed the existence of an original ncRNA-dependent pathway that controls gene expression in S. cerevisiae. In the light of our results we proposed that a class of unstable ncRNA can mediate genome stabilization through epigenetic modifications.
With this project, we draw the first exhaustive catalog of yeast antisense lncRNA using original High throughput technologies and bioinformatics pipelines. Second, we described further mechanistic insights into the functional role of antisense lncRNA on genome expression and stability. Our data showed the existence of an entire class of antisense regulatory lncRNA extremely sensitive to RNA decay pathways, impinging their study so far. The roles for yeast antisense lncRNAs in shaping the epigenome paved the way for future fundamental studies: We propose that the dark side of the non-coding genome is another layer of gene regulation complexity that needs to be deciphered.
With this project, we draw the first exhaustive catalog of yeast antisense lncRNA using original High throughput technologies and bioinformatics pipelines. Second, we described further mechanistic insights into the functional role of antisense lncRNA on genome expression and stability. Our data showed the existence of an entire class of antisense regulatory lncRNA extremely sensitive to RNA decay pathways, impinging their study so far. The roles for yeast antisense lncRNAs in shaping the epigenome paved the way for future fundamental studies: We propose that the dark side of the non-coding genome is another layer of gene regulation complexity that needs to be deciphered.