@article {Cid-Samper298943, author = {Fernando Cid-Samper and Mariona Gelabert-Baldrich and Benjamin Lang and Nieves Lorenzo-Gotor and Riccardo Delli Ponti and Lies-Anne WFM Severijnen and Benedetta Bolognesi and Ellen Gelpi and Renate K. Hukema and Teresa Botta-Orfila and Gian Gaetano Tartaglia}, title = {An integrative study on ribonucleoprotein condensates identifies scaffolding RNAs and reveals a new player in Fragile X-associated Tremor/Ataxia Syndrome}, elocation-id = {298943}, year = {2018}, doi = {10.1101/298943}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Recent evidence indicates that specific RNAs promote formation of ribonucleoprotein condensates by acting as scaffolds for RNA-binding proteins (RBPs).We systematically investigated RNA-RBP interaction networks to understand ribonucleoprotein assembly. We found that highly-contacted RNAs are highly structured, have long untranslated regions (UTRs) and contain nucleotide repeat expansions. Among the RNAs with such properties, we identified the FMR1 3{\textquoteright} UTR that harbors CGG expansions implicated in Fragile X-associated Tremor/Ataxia Syndrome (FXTAS).We studied FMR1 binding partners in silico and in vitro and prioritized the splicing regulator TRA2A for further characterization. In a FXTAS cellular model we validated TRA2A-FRM1 interaction and investigated implications of its sequestration at both transcriptomic and post-transcriptomic levels. We found that TRA2A co-aggregates with FMR1 in a FXTAS mouse model and in post mortem human samples.Our integrative study identifies key components of ribonucleoprotein aggregates, providing links to neurodegenerative disease and allowing the discovery of new therapeutic targets.}, URL = {https://www.biorxiv.org/content/early/2018/11/12/298943}, eprint = {https://www.biorxiv.org/content/early/2018/11/12/298943.full.pdf}, journal = {bioRxiv} }