Project description DEENESFRITPL Unlocking secrets of mammalian RNAi features Viral infections in the genome often produce double-stranded RNA (dsRNA) that can be targeted by RNase III Dicer in the RNA interference (RNAi) pathway. While endogenous mammalian RNAi is present, its physiological characteristics and functions are not fully understood. One reason for this is the inefficient processing of dsRNA by the full-length Dicer, which contributes to mammalian RNAi dormancy. To better understand RNAi function in the germline and assess the antiviral activity of RNAi for animal farming and human therapy, the D-FENS project, funded by the European Research Council, will explore the physiological significance of the N-terminal part of Dicer using genetic animal models. This research aims to uncover species-specific features of RNAi and improve our understanding of its common and unique characteristics. Show the project objective Hide the project objective Objective Viral infection or retrotransposon expansion in the genome often result in production of double-stranded RNA (dsRNA). dsRNA can be intercepted by RNase III Dicer acting in the RNA interference (RNAi) pathway, an ancient eukaryotic defense mechanism. Notably, endogenous mammalian RNAi appears dormant while its common and unique physiological roles remain poorly understood. A factor underlying mammalian RNAi dormancy is inefficient processing of dsRNA by the full-length Dicer. Yet, a simple truncation of Dicer leads to hyperactive RNAi, which is naturally present in mouse oocytes.The D-FENS project will use genetic animal models to define common, cell-specific and species-specific roles of mammalian RNAi. D-FENS has three complementary and synergizing objectives:(1) Explore consequences of hyperactive RNAi in vivo. A mouse expressing a truncated Dicer will reveal at the organismal level any negative effect of hyperactive RNAi, the relationship between RNAi and mammalian immune system, and potential of RNAi to suppress viral infections in mammals.(2) Define common and species-specific features of RNAi in the oocyte. Functional and bioinformatics analyses in mouse, bovine, and hamster oocytes will define rules and exceptions concerning endogenous RNAi roles, including RNAi contribution to maternal mRNA degradation and co-existence with the miRNA pathway.(3) Uncover relationship between RNAi and piRNA pathways in suppression of retrotransposons. We hypothesize that hyperactive RNAi in mouse oocytes functionally complements the piRNA pathway, a Dicer-independent pathway suppressing retrotransposons in the germline. Using genetic models, we will explore unique and redundant roles of both pathways in the germline.D-FENS will uncover physiological significance of the N-terminal part of Dicer, fundamentally improve understanding RNAi function in the germline, and provide a critical in vivo assessment of antiviral activity of RNAi with implications for human therapy. Fields of science medical and health sciencesmedical biotechnologygenetic engineeringmedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological scienceszoologymammalogymedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-CoG-2014 - ERC Consolidator Grant Call for proposal ERC-2014-CoG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Coordinator USTAV MOLEKULARNI GENETIKY AKADEMIE VED CESKE REPUBLIKY VEREJNA VYZKUMNA INSTITUCE Net EU contribution € 1 537 000,00 Address Videnska 1083 142 20 Praha 4 Czechia See on map Region Česko Praha Hlavní město Praha 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 (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all USTAV MOLEKULARNI GENETIKY AKADEMIE VED CESKE REPUBLIKY VEREJNA VYZKUMNA INSTITUCE Czechia Net EU contribution € 1 537 000,00 Address Videnska 1083 142 20 Praha 4 See on map Region Česko Praha Hlavní město Praha 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 SLOVENSKA ZDRAVOTNICKA UNIVERZITA V BRATISLAVE Slovakia Net EU contribution € 413 000,00 Address Limbova 12 833 03 Bratislava See on map Region Slovensko Bratislavský kraj Bratislavský kraj 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
