Project description DEENESFRITPL Ribonucleoproteins remodelling in development and disease A ribonucleoprotein (RNP) is a complex of ribonucleic acid and RNA-binding protein. These complexes play an integral part in important biological functions including DNA replication, gene expression regulation and RNA metabolism. Some mutations causing cancer or neurodegenerative diseases (such as amyotrophic lateral sclerosis) occur in RNA-binding proteins. These mutations are concentrated in the intrinsically disordered regions of the proteins which lack a well-defined 3D structure but play important roles in protein regulation, including RNP assembly and disassembly. The EU-funded RNPdynamics project will build a framework of experimental and computational methods to study the mechanisms of RNP remodelling, and to explore how such RNP dynamics contribute to cellular transitions in development and disease. Show the project objective Hide the project objective Objective Ribonucleoprotein complexes (RNPs) play many key regulatory roles in development. Moreover, mutations causing cancer or neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), often occur in RNA-binding proteins (RBPs). These mutations are concentrated in the intrinsically disordered regions (IDRs), which play a central role in the control of RNP assembly and disassembly. RNP dynamics is often driven by multivalent interactions that are mediated by multiple elements within IDRs of RBPs, which can condense the RNP such that it separates from the surrounding liquid through the phenomenon of liquid-liquid phase separation. Transcriptomic insights into the physiological functions of such multivalent RNP assembly are needed to understand their regulation, or deregulation through disease-causing mutations. Here, we will build a framework of experimental and computational methods to study the mechanisms by which the dynamic multivalent interactions drive RNP remodelling, and how such RNP dynamics contributes to cellular transitions in development and disease. The first objective will be to identify the functions of specific RBPs in cell-state transitions during neuronal differentiation, and the mechanisms of IDR-mediated multivalent interactions in these functions. The next objective will be to establish new tools to manipulate RNP assembly through multivalent RNA binding sites and IDRs. Finally, the new insights and tools will be integrated with the goal to fine-tune the RNP assembly of ALS-mutant RBPs, and thereby ameliorate their toxicity. Fields of science natural sciencescomputer and information sciencescomputational sciencenatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsRNAmedical and health sciencesbasic medicineneurologyamyotrophic lateral sclerosis Keywords GBP: GFP-binding protein (nanobody) IDR: intrinsically disordered region LINE: long interspersed nuclear element LLPS: liquid-liquid phase separation RBP: RNA binding protein RNP: ribonucleoprotein complex RTE: retrotransposable element SLiM: short linear motif Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2018-ADG - ERC Advanced Grant Call for proposal ERC-2018-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Coordinator KEMIJSKI INSTITUT Net EU contribution € 1 827 418,25 Address Hajdrihova 19 1000 Ljubljana Slovenia See on map Region Slovenija Zahodna Slovenija Osrednjeslovenska Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (4) Sort alphabetically Sort by Net EU contribution Expand all Collapse all KEMIJSKI INSTITUT Slovenia Net EU contribution € 1 827 418,25 Address Hajdrihova 19 1000 Ljubljana See on map Region Slovenija Zahodna Slovenija Osrednjeslovenska Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 UNIVERSITY COLLEGE LONDON Participation ended United Kingdom Net EU contribution € 359 515,00 Address Gower street WC1E 6BT London See on map Region London Inner London — West Camden and City of London Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure. THE FRANCIS CRICK INSTITUTE LIMITED Participation ended United Kingdom Net EU contribution € 160 735,00 Address 1 midland road NW1 1AT London See on map Region London Inner London — West Camden and City of London Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 KING'S COLLEGE LONDON United Kingdom Net EU contribution € 48 593,00 Address Strand WC2R 2LS London See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
