RIBOMYLOME

A major portion of the eukaryotic genome is occupied by DNA sequences whose transcripts do not code for proteins. This part of the genome is transcribed in a developmentally regulated manner and in response to external stimuli to produce large numbers of long non-coding RNAs (lncRNAs). Characterizing protein-RNA associations is key to unravel the complexity and functionality of mammalian genomes and could open up new therapeutic avenues for the treatment of a broad range of neurodegenerative disorders. In this project, I propose to study associations of lncRNAs with proteins involved in i) transcriptional regulation and epigenetics (such as polymerases, transcription factors and chromatin-modifiers) and ii) neurodegenerative diseases (such as Parkinson’s-synuclein, Alzheimer’s disease amyloid protein APP, TDP-43 and FUS).  In particular, I will investigate if RNA molecules are involved in regulatory mechanisms that control protein production and prevent formation of toxic aggregates. In a multidisciplinary effort, I aim to discover protein-RNA interactions using advanced computational methods developed in my group and state of the art experimental techniques such as electromobility shift, filter binding assays and RNA-binding protein immunopurification-microarrays as well as Thioflavin T fluorescence spectroscopy, size exclusion chromatography and trasmission electron microscopy.