Sandra L. Wolin, M.D., Ph.D.

Professor of Cell Biology and Molecular Biophysics & Biochemistry We are elucidating noncoding RNA quality pathways and determining how the failure to degrade defective RNAs impacts cell function.
Wolin lab website Phone: (203) 737-4439 Lab: (203) 737-4426 Fax: (203) 737-1761 e-mail: sandra.wolin@yale.edu		Department of Cell Biology Yale Universtiy School of Medicine 333 Cedar Street PO Box 208002 New Haven, CT 06520-8002 <Courier Address> 295 Congress Avenue, BCMM 154B (Lab: BCMM 139/141) New Haven, CT 06519-1418

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Our laboratory studies how cells recognize and handle misfolded, damaged and unneeded RNAs and how the failure to degrade these RNAs impacts cell function and disease.  In mammalian cells, yeast and bacteria, we focus on proteins and noncoding RNAs that play critical roles in these processes.

 

In one project, we study how misfolded and defective noncoding RNAs are recognized and targeted for decay in mammalian cells.  One of the pathways that we study involves a ring-shaped protein called Ro that binds misfolded RNAs in its central cavity.  Because mice lacking Ro develop an autoimmune disease resembling human lupus, Ro may be important for preventing autoimmunity.  Interestingly, we have found that non-coding RNAs called Y RNAs influence the association of Ro with both defective RNAs and protein partners.  We are examining the various components of the Ro pathway and determining how the Ro pathway interfaces with other nuclear RNA surveillance pathways.  In a second focus, we are using genetics and biochemistry in yeast to identify components that are important for handling damaged RNAs. Our experiments utilize a wide variety of techniques, including mammalian cell culture, yeast genetics, biochemistry, microscopy, and structural biology.

Figure 1.  Structure of the Ro protein.  Ro is shaped like a doughnut with a central hole.  In
this space-filling representation, positively charged surfaces are colored blue and negatively charged surfaces are red.  The 3’ ends of misfolded RNA insert through the hole, which may assist in their subsequent degradation by exonucleases.

Selected Publications

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Wurtmann, E.J. and Wolin, S.L. (2009).  RNA Under Attack: Cellular Handling of RNA Damage. Crit. Rev. Biochem. Mol. Biol. 44, 34-49.

Sim, S., Weinberg, D.E., Fuchs, G., Choi, K., Chung, J. and Wolin, S.L. (2009). The Subcellular Distribution of an RNA Quality Control Protein, the Ro Autoantigen, is Regulated by Noncoding Y RNA Binding.  Mol. Biol. Cell 20, 1555-64.

Garcia, E.L., Onafuwa-Nuga, A., Sim, S., King, S.R., Wolin, S.L. and Telesnitsky, A. (2009). Packaging of Host Y RNAs by Murine Leukemia Virus May Occur Early in Y RNA Biogenesis, J. Virology, in press.

Copela, L.A., Fernandez, C.F., Sherrer, R.L. and Wolin, S.L. (2008).  Competition between the Rex1 Exonuclease and the La Protein Affects Both Trf4p-mediated RNA Quality Control and Pre-tRNA Maturation.  RNA 14, 1214-1227.

Chen, X., Wurtmann, E.J., Van Batavia, J., Zybailov, B., Washburn, M.P. and Wolin, S.L. (2007).  An Orthologue of the Ro Autoantigen Functions in 23S rRNA Maturation in D. radiodurans.  Genes & Dev. 21, 1328-1339.

Fuchs G, Stein AJ, Fu C, Reinisch KM and Wolin SL. (2006)  Structural and Biochemical Basis for Misfolded RNA Recognition by the Ro Protein. Nat. Struct. Mol. Biol., 13, 1002-1009.

Wolin SL and Reinisch KM. (2006)  The Ro 60 kDa Autoantigen Comes into Focus:  Interpreting Epitope Mapping Experiments on the Basis of Structure.  Autoimmunity Reviews 5, 367-372.

Stein AJ, Fuchs G, Fu C, Wolin SL, Reinisch KM. (2005)  Structural Insights into RNA Quality Control: The Ro Autoantigen Binds Misfolded RNAs via its Central Cavity. Cell 121: 529-539.