Molecular movies of large non-coding RNAs assembling into functionally-active 3D structures

Many non-coding RNAs (ncRNAs) rely on three-dimensional (3D) structures to perform their cellular functions, but the underlying mechanisms by which RNAs acquire 3D structures are still poorly characterized.

Capitalizing on nucleotide-resolution chemical probing data, cell-based functional assays, and preliminary cryoEM structures, here we will produce molecular movies of two prototypical large ncRNAs in the process of sequentially assembling, domain-by-domain, into their functionally-active 3D structures.

Our near-atomic resolution insights will help rationalize the absolutely-essential functional role played by conserved sequence and structured motifs in guiding the assembly of our RNA targets. Moreover, our data will crucially unveil novel allosteric druggable sites in these medically-important targets.

More broadly, our work will establish the methodology to study the dynamics of very large RNAs at high-resolution, and will derive generalizable principles of RNA folding thus contributing to unravel the structure-functional complexity of the non-coding transcriptome.