LncRNA scaffolds of nuclear RNP compartments, and their roles in embryogenesis. (360G-Wellcome-218672_Z_19_Z)
Several long non-coding RNAs (lncRNAs) are capable of scaffolding ribonucleoproteins (RNPs) that condense and phase-separate nuclear membraneless compartments. Both, lncRNAs and RNPs play many key regulatory roles in development and their function in cell fate choice is further enhanced by their cross-regulation. To demonstrate the importance of such cross-regulation for fine-tuning developmental decisions I will build a framework of experimental and computational methods to study how lncRNAs scaffold nuclear RNP compartments and hence understand how interactions between lncRNAs and RNPs within these compartments create networks that coordinate molecular processes in early development. To interrogate the developmental role of these network motifs between lncRNAs and bound RNPs, I will also establish new tools that allow rapid manipulation of lncRNA condensation in advanced in-vitro embryogenesis system. Collectively, this proposal will reveal the cross-regulatory mechanism of nuclear rewiring by lncRNA condensation that plays a role not only in development, but when perturbed, could also be implicated in diseases such as ALS and cancer.
£300,000 06 Nov 2019