Sandra L Wolin MD, PhD

Professor of Cell Biology and of Molecular Biophysics and Biochemistry; Director, Yale Center for RNA Science and Medicine

Research Interests

Noncoding RNAs; RNA surveillance; RNA damage; Autoimmune disease; Environmental stress

Research Summary

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.

Selected Publications

  • Eckwahl, M.J., Sim, S., Smith, D., Telesnitsky, A. and Wolin, S.L. (2015). A retrovirus packages host noncoding RNAs from a novel surveillance pathway. Genes and Development 29, 646-57.
  • Chen, X., Sim, S., Wurtmann, E.J., Feke, A. and Wolin, S.L. (2014). Bacterial noncoding Y RNAs are widespread and mimic tRNAs. RNA 20, 1715-24.
  • Chen, X., Taylor, D.W., Fowler, C.C., Galan, J.E., Wang, H.-W., Wolin, S.L. (2013). An RNA degradation machine sculpted by Ro autoantigen and noncoding RNA. Cell 153, 166-177.
  • Wolin, S.L., Sim, S. and Chen, X. (2012). Nuclear noncoding RNA surveillance: is the end in sight? Trends Genet. 28, 306-313.
  • Sim, S., Yao, J., Weinberg, D.E., Niessen, S., Yates, JR 3rd and Wolin, S.L. (2012). The zipcode-binding protein ZBP1 influences the subcellular location of the Ro 60-kDa autoantigen and the noncoding Y3 RNA. RNA 18, 100-110.
  • Kucera, N.J., Hodsdon, M.E. and Wolin, S.L. (2011). An intrinsically disordered C-terminus allows the La protein to assist the biogenesis of diverse noncoding RNA precursors. Proc. Natl. Acad. Sci. USA 108, 1308-13.

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