000204469 001__ 204469
000204469 005__ 20230212173728.0
000204469 0247_ $$2CORDIS$$aG:(EU-Grant)747488$$d747488
000204469 0247_ $$2CORDIS$$aG:(EU-Call)H2020-MSCA-IF-2016$$dH2020-MSCA-IF-2016
000204469 0247_ $$2originalID$$acorda__h2020::747488
000204469 035__ $$aG:(EU-Grant)747488
000204469 150__ $$aFunctional dissection of core spliceosomal mutations causing Retinitis Pigmentosa.$$y2017-04-01 - 2019-03-31
000204469 371__ $$aFUNDACIO CENTRE DE REGULACIO GENOMICA$$dSpain$$ehttp://www.crg.es$$vCORDIS
000204469 372__ $$aH2020-MSCA-IF-2016$$s2017-04-01$$t2019-03-31
000204469 450__ $$aSpliceCore$$wd$$y2017-04-01 - 2019-03-31
000204469 5101_ $$0I:(DE-588b)5098525-5$$2CORDIS$$aEuropean Union
000204469 680__ $$aMore than 95% of human genes undergo pre-mRNA splicing, and alternative splicing of mRNA precursors represents a prevalent mode of gene regulation. Errors in this process are often the origin of of disorders. Most of splicing-related diseases are caused by perturbation in pre-mRNA transcripts which lead to their aberrant processing. Interestingly, a fraction of mutations affecting directly splicing factors, including core spliceosomal components, has been linked to a group of pathologies. Particularly intriguing are variants of the key spliceosomal subcomplex U4/5/6 tri-snRNP, associated with Retinitis Pigmentosa. Why these mutations lead to highly tissue-specific phenotypes, rather than general toxicity cause by a global block in splicing, remain unexplained. The proposed research aims to increase our understanding of the molecular mechanisms underlying the effects of these mutations and shed light on the basis of the disease. To functionally dissect these variants, I will combine spliceosomal network approaches (I) with genome-wide transcriptome analysis (II) and detailed biochemical and structural studies (III). Mechanistic insights derived from these analyses will help to identify transcripts that are predominantly sensitive to these mutations and that could be behind their pathogenic effects (IV). This work will allow us to better understand the function of key splicing factors, as well as the basis for their effects on splice site selection and their contributions to Retinitis Pigmentosa pathology.
000204469 909CO $$ooai:juser.fz-juelich.de:833246$$pauthority$$pauthority:GRANT
000204469 909CO $$ooai:juser.fz-juelich.de:833246
000204469 970__ $$aoai:dnet:corda__h2020::6c9b2581c828758efcb936e03241c4fa
000204469 980__ $$aG
000204469 980__ $$aCORDIS
000204469 980__ $$aAUTHORITY