Sandra L Wolin MD, PhD
Professor of Cell Biology and of Molecular Biophysics and Biochemistry; Director, Yale Center for RNA Science and Medicine
Noncoding RNAs; RNA surveillance; RNA damage; Autoimmune disease; Environmental stress
Noncoding RNAs are involved in an enormous variety of processes. In addition to well-studied noncoding RNAs, such as ribosomal RNAs, tRNAs, and microRNAs, there are numerous noncoding RNAs whose function remains mysterious. Also, many noncoding RNAs must fold into complicated structures and assemble with proteins in order to function. Thus, cells need “RNA surveillance” mechanisms to detect misfolded and defective noncoding RNAs and target them for degradation.
We study how noncoding RNAs function, how cells recognize and degrade defective RNAs, and how failure to degrade RNA affects cells and contributes to disease. One pathway involves a ring-shaped protein, called Ro, that binds misfolded RNAs in its central cavity and noncoding RNAs called Y RNAs on its outer surface. Ro and Y RNAs are present in both animal cells and bacteria, and we discovered that a bacterial Ro and Y RNA associate with a nuclease to form a new RNA degradation machine. As mice lacking Ro develop a disease resembling systemic lupus erythematosus, Ro may be important for preventing autoimmunity. In a second effort, we are characterizing other RNA surveillance pathways in mammalian cells. We use many techniques, including cell culture, high-throughput sequencing, bioinformatics, mouse and bacterial genetics, biochemistry and cell imaging.