uTSSreg · Regulation of mammalian genes by new classes of promoter proximal transcription start sites

Regulation of mammalian genes by new classes of promoter proximal transcription start sites

The development of high-throughput sequencing methods has revealed that mammalian genomes have complex transcription patterns that generate far more spurious transcripts than RNA molecules from conventional protein-coding genes. However, the extent and content of the information encoded by such extensive transcription and the functions that the generated noncoding RNA can perform remain to be understood. RNA exosomes are evolutionarily conserved multisubunit complexes of 9 core subunits, including RRP40, with 3 '-5' exo- and endo- nucleolytic activities and in many cases, have been shown to eliminate spurious transcripts from the nucleus rapidly. Interestingly, unpublished data recently from my lab shows that there are multiple transcription start sites (TSSs) in the promoter region, many of which produce exosome-sensitive products in hundreds of cases. Therefore, there may be previously unknown transcriptional events associated with promoters that affect the regulation of gene activity. Collecting these examples and studying the mechanisms makes it possible to discover entirely new principles of gene regulation and elucidate the molecular mechanisms underlying them. Understanding these new mechanisms is also of great importance in the related fields of developmental biology and medicine. The overarching aim of the proposed project is to locate spurious transcription events and to investigate the impact of selected cases on local gene expression. Employing rapid depletion of nuclear RNA decay activities, I will construct a comprehensive map of transcription events, which are normally 'hidden' by RNA turnover, therefore producing unstable TSSs (uTSSs).

Data: CORDIS, © European Union