Cid Samper, Fernando, 1991-Gelabert-Baldrich, MarionaLang, BenjaminLorenzo Gotor, Maria de las NievesPonti, Riccardo delliSeverijnen, Lies-Anne W.F.M.Bolognesi, BenedettaGelpi, EllenHukema, Renate K.Botta Orfila, TeresaTartaglia, Gian Gaetano2019-11-042019-11-042018Cid-Samper F, Gelabert-Baldrich M, Lang B, Lorenzo-Gotor N, Ponti RD, Severijnen LWFM et al. An integrative study of protein-RNA condensates identifies scaffolding RNAs and reveals players in fragile X-associated tremor/ataxia syndrome. Cell Rep. 2018; 25(12):3422-34. DOI: 10.1016/j.celrep.2018.11.0762211-1247http://hdl.handle.net/10230/42588Recent evidence indicates that specific RNAs promote the 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 structured, have long UTRs, and contain nucleotide repeat expansions. Among the RNAs with such properties, we identified the FMR1 3' 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 the TRA2A-FMR1 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 therapeutic targets.application/pdfeng© 2018 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)info:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.celrep.2018.11.076Phase separationScaffolding RNACGG repeat expansionFMR1 premutationFragile X-associated tremor/ataxia syndromeFXTASRNA aggregatesRNA binding proteinsRBPTRA2A splicing regulatorNeurodegenerationinfo:eu-repo/semantics/openAccess