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Dark matter of the human transcriptome: Functional study of the antisense Long Noncoding RNAs and Molecular Mechanisms of Action

Final Report Summary - DARK (Dark matter of the human transcriptome: Functional study of the antisense Long Noncoding RNAs and Molecular Mechanisms of Action)

98% of the eukaryote’s genome is non-protein coding raising the question of the role of the dark matter of the genome. Pervasive transcription generates thousands of noncoding transcripts having immediate 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. One of the reasons of the lack of information is their low expression and difficulties to be measured in vivo.
With this project, we draw a novel catalog of the human lncRNA including antisense using original High throughput technologies and bioinformatics pipelines. Strikingly, we show that these novel lncRNAs can be used as efficient biomarkers for prostate cancer diagnosis. Second, we propose a dissection of the functional role the antisense lncRNA HOTAIR during chronic DNA damage through its multimodal platform of proteins interaction. In addition, our unpublished data propose the existence of an entire class of cryptic cytoplasmic lncRNA sensitive to the RNA decay pathway DIS3, impinging their study so far. The roles for antisense lncRNAs in shaping the epigenome paved the way for future fundamental and structural studies but also enlarge our vision for novel biomarkers in cancer.