Project description DEENESFRITPL Uncovering the nuclear export mechanism of piRNA precursors The export of newly synthesised RNA to the cytoplasm from the nucleus is a critical stage of eukaryotic gene expression. The EU-funded RNA Smuggling project plans to study the RNA export of a family of long non-coding RNAs and elucidate fundamental principles underlying the regulated assembly of export-competent ribonucleoproteins. Research will be geared towards the precursors of a class of small regulatory RNAs: piRNAs. Notably, piRNA precursors bend canonical gene expression rules by violating mRNA quality control checkpoints. Revealing how they bypass nuclear RNA surveillance mechanisms will boost our understanding of RNA cargo loading onto nuclear export family proteins and the molecular principles underlying nuclear RNA export. Show the project objective Hide the project objective Objective Nuclear export of newly synthesized RNA to the cytoplasm is an essential step in eukaryotic gene expression, yet the participating proteins and their interplay remain poorly understood at the molecular level. Here, I propose to study RNA export of a family of long non-coding RNAs to elucidate fundamental principles underlying the regulated assembly of export-competent RNPs. I will focus on the precursors of piRNAs, a class of small regulatory RNAs. These transcripts are generated by RNA Polymerase II from heterochromatic, transposon-rich loci and are processed into piRNAs in the cytoplasm to specify transposon silencing. Notably, piRNA precursors violate mRNA quality control hallmarks and thus have to bypass degradation in the nucleus for their export. For this a specialized pathway evolved, combining canonical mRNA export factors with novel or neo-functionalized components. I propose a holistic approach combining quantitative biochemistry, structural biology and genetics to integrate known and novel components into a coherent model of piRNA-precursor export. I aim at understanding (1) the recruitment of export factors to sites of transcription, and (2) the nature and regulation of a nuclear piRNP complex consisting of piRNA factors and the canonical mRNA export components UAP56 and THO complex. The molecular function and regulation of these highly conserved proteins is poorly understood. Elucidating how piRNA-precursor export hijacks canonical RNA export factors to avoid mRNA quality control thus holds great promise to uncover general principles of RNA cargo loading onto NXF family proteins and the molecular principles of nuclear RNA export. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological sciencesmolecular biologystructural biology Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2019 - Individual Fellowships Call for proposal H2020-MSCA-IF-2019 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH Net EU contribution € 174 167,04 Address Dr bohrgasse 3 1030 Wien Austria See on map Region Ostösterreich Wien Wien Activity type Private for-profit entities (excluding 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
