RNA molecules play critical and diverse roles in a staggering number of cellular processes. Processes of particular interest in the department include determining how cells recognize and handle defective RNAs, how RNA-binding proteins recognize their RNA targets, how mRNAs are localized to discrete regions of cells and how small noncoding RNAs influence gene expression, cell function, and stem cell biology.
Many RNAs must fold into complex structures and assemble with proteins in order to function. Yet, little is known as to how RNA folding is accomplished in vivo or how cells recognize and handle misfolded RNAs. The identification of proteins that act as molecular chaperones to assist RNA folding is underway, as is the study of a newly discovered quality control pathway for noncoding RNAs. Interestingly, recent results suggest links between the failure of RNA quality control mechanisms and the development of autoimmune disease.
Just as RNAs come in all shapes and sizes, the proteins that recognize them use a diversity of motifs to distinguish one RNA from another. Structural studies underway address how RNA-binding proteins stabilize newly synthesized RNAs and assist their folding, and how proteins distinguish correctly folded RNAs from misfolded species.
Small noncoding RNAs influence many cellular processes, from transcription and chromosome replication to RNA processing and protein secretion. Most recently, very short (~20-30 nt) noncoding RNAs have been found to silence gene expression in a large number of eukaryotic organisms. This discovery has stimulated an incredible wave of interest in RNA-mediated gene silencing. The goals are to investigate the mechanism and components of the pathway and to understand how the specific interactions between short noncoding RNAs and their target mRNAs are brought about. Another area of research is focused on understanding the roles of a newly discovered class of noncoding RNAs, called piRNAs, in stem cell self-renewal.
mRNA localization plays a key role in cell differentiation and in the regulation of synaptic connections between neurons. Cells often use molecular motors to transport mRNAs along cytoskeletal filaments. Experiments are underway to determine the molecular mechanisms by which mRNAs and motor proteins interact.