Macro non-coding RNAs as epigenetic regulators in human disease

The classic view of the flow of genetic information, "gene - mRNA - protein" has experienced a change to "gene - RNA - function". Many RNAs are now known to be terminal gene products that exert their functions in different ways: regulating other RNAs and proteins, catalysing chemical reactions, guiding RNAs to their place of action, or silencing small genomic regions or whole chromosomes. Using model organisms as diverse as bacteria, ciliates, insects, plants and mammals, this RNA-REG SFB will study how RNA regulates the flow of genetic information. All cellular processes that affect the transcriptome and are modulated by regulatory RNAs, - from epigenetic phenomena, chromatin structure and transcription to RNA processing, transport, decay and translation - will be analysed in depth with the goal of defining the RNA regulon. The unifying theme of this RNA-REG SFB is to reveal the function of regulatory RNAs, understand the mechanism(s) by which these regulations are achieved and how diverse RNA-mediated processes interconnect to result in the observed phenotypes. This will shed light on how RNAs control the flow of genomic information and how these RNAs are regulated themselves and ultimately, allow a molecular understanding of developmental dysfunctions and diseases that arise from errors in these circuits. Fifteen groups from six institutions working on the diverse aspects of RNA biology are pooling their expertises and experiences to reach this goal. Technical progress in deep sequencing, mapping RNA-protein interactions and biocomputing, together with the emerging view that RNAs regulate most biological processes, make this RNA- centric SFB timely, because they allow the application of unbiased large-scale approaches to unravel the full degree of complexity in RNA mediated processes in the cell.