home > faculty > wolin

SANDRA WOLIN

RNA folding and misfolding inside cells; RNA quality control; RNA chaperones
We study how RNA molecules fold into intricate structures inside cells, how cells recognize and handle misfolded RNAs, and the consequences of RNA misfolding for cell physiology and disease. In mammalian cells, yeast, and bacteria, we focus on proteins and RNA-protein complexes that play critical roles in RNA folding and quality control. Our experiments utilize a wide variety of techniques and approaches, including biochemistry, cell biology, yeast and bacterial genetics, and structural biology. Interestingly, our work has revealed unexpected connections between RNA quality control, survival after radiation exposure, and autoimmune disease.

A novel RNA quality control pathway in mammalian cells and bacteria
In one project, we study the Ro protein, which binds misfolded noncoding RNAs that are targeted for decay. In collaboration with Karin Reinisch, we demonstrated that Ro is shaped like a donut with a central hole. The 3' single-stranded ends of misfolded RNAs bind inside the central cavity, while helical portions bind on the outer surface. Interestingly, we recently discovered that the binding of misfolded RNAs to Ro is likely regulated by noncoding RNAs called Y RNAs. As both mammalian and bacterial cells lacking Ro are sensitive to ultraviolet irradiation, we are examining whether Ro is also involved in the decay of radiation-damaged RNAs. We are also characterizing the various functions of Ro in mouse and bacterial cells. Amazingly, mice lacking Ro develop an autoimmune disease that resembles systemic lupus erythematosus in patients. As Ro is a major target of the immune response in lupus patients, this result raises the possibility that lack of Ro function contributes to autoimmune disease in humans.

Uncovering novel RNA quality control components in yeast
In a second effort, we are using biochemistry and genetics in the yeast Saccharomyces cerevisiae to identify novel components of RNA quality control pathways and to understand how known quality control pathways interface with RNA chaperones. One focus is the La protein, which binds many newly synthesized noncoding RNAs and functions as an "RNA chaperone" to assist small RNA folding and RNA-protein complex assembly.

Selected Publications

Fernandez, C., Pannone, B.K., Chen, X., Fuchs, G. and Wolin, S.L. An Lsm2-Lsm7 Complex Associates with the Yeast Small Nucleolar RNA snR5. Mol. Biol. Cell 15, 2842-2852 (2004)

Stein, A.J., Fuchs, G., Fu, C., Wolin, S.L., and Reinisch, K.M. Structural Insights into RNA Quality Control: The Ro Autoantigen Binds Misfolded RNAs via its Central Cavity. Cell 121, 529-539 (2005)

Fuchs, G., Stein, A.J., Fu, C., Reinisch, K.M. and Wolin, S.L. Structural and Biochemical Basis for Misfolded RNA Recognition by the Ro Protein. Nat. Struct. Mol. Biol. 11, 1002-1009 (2006)

Copela, L.A., Chakshusmathi, G., Sherrer, R.L., and Wolin, S.L. The La Protein Functions Redundantly with tRNA Modification Enzymes to Ensure tRNA Structural Stability. RNA 12, 644-654 (2006)

Chen, X., Wurtmann, E.J., Van Batavia, J., Zybailov, B. Washburn, M.P. and Wolin, S. L.  An orthologue of the Ro autoantigen functions in 23S rRNA maturation in D. radiodurans.  Genes & Dev. 21, 1328-39 (2007)

Last Updated 06-25-07