Grant: Project Grant

RNAs are long, single-stranded polymers composed of nucleic acids, generally much longer than proteins' amino acid chains. RNAs are also very versatile biomolecules as they fulfill many functions in the cell, such as being temporary copies of the genetic information read by ribosomes to make proteins or as a structural and catalytic component of the protein synthesis machinery, the ribosome itself. Due to the large size of many cellular RNAs, these RNAs form complex three-dimensional assemblies; however, the overall structural organization, i.e., their topology, as well as the mechanisms and rules that define RNA topology of most RNAs, is only poorly understood and has not been extensively studied. RNA topology, however, is central to RNA's function, and deciphering the mechanisms that modulate RNA topology is one of the last remaining challenges in RNA biology. The aim of this proposal is to use various microscopy, genetic, computational, and proteomic-based approaches to investigate features and dynamics of RNA topology and RNA-protein complexes and the role of RNA topology in modulating RNA metabolism, in particular two steps along the gene expression pathway, pre-mRNA splicing and translation, both critical steps of gene expression misregulated in many disease states. Our study will, therefore, also contribute important new knowledge to find entry points for future research, therapies, and treatment of various diseases affected by the misregulation of gene regulatory processes.