| Professor of Cell Biology and Molecular Biophysics & Biochemistry |
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| Wolin lab website Phone: (203) 737-4439 Lab: (203) 737-4426 Fax: (203) 737-1761 e-mail: sandra.wolin@yale.edu |
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Department of Cell Biology <Courier Address> |
The Ro protein: a protein that binds misfolded RNAs is important for cell survival after ultraviolet irradiation and for prevention of autoimmunity
The Ro protein is a major autoantigen in patients with the autoimmune disease systemic lupus erythematosus. We have discovered that the Ro protein binds misfolded small RNAs in vertebrate cells. Moreover, the Ro protein is part of a novel mechanism by which cells survive stresses such as irradiation with ultraviolet light. Most interestingly, mice lacking the Ro protein develop an autoimmune disease that resembles systemic lupus erythematosus. We are examining the role of the Ro protein in helping cells survive irradiation and other stresses. We are also studying how the Ro protein interfaces with the known pathways that cells use to respond to stress.
Figure: The Ro protein accumulates in the nucleus following ultraviolet irradiation. Using immunofluorescence, we determined the distribution of the Ro protein in mouse fibroblasts before (left) and after irradiation (right) (from Chen et al., 2003).
Selected Publications:
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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.
Dong G, Chakshusmathi G, Wolin SL, Reinisch K. (2004) Structure of the La Motif: A Winged Helix Domain Mediates RNA Binding Via a Conserved Aromatic Patch. EMBO J. 23: 1000-1007.
Chen X and Wolin SL. (2004) The Ro 60 kDa Autoantigen: Insights Into Cellular Function And Role In Autoimmunity. J. Mol. Med. 82: 232-239.
Fernandez C, Pannone BK, Chen X, Fuchs G, Wolin SL. (2004) An Lsm2-Lsm7 Complex Associates with the Yeast Small Nucleolar RNA snR5. Mol. Biol. Cell 15: 2842-52.
Chakshusmathi G, Kim SD, Rubinson DA, and Wolin SL. (2003) A La Protein Requirement for Efficient Pre-tRNA Folding. EMBO Journal 22: 6562-6572.
Chen X, Smith JD, Shi H, Yang DD, Flavell RA, Wolin SL (2003) The Ro 60 kDa Autoantigen Binds Misfolded U2 Small Nuclear RNAs and Assists Mammalian Cell Survival Following Ultraviolet Irradiation. Curr Biol. 13: 2206-2211.
Xue D, Shi H, Smith JD, Chen X, Noe DA, Cedervall T, Yang DD, Eynon E, Brash DE, Kashgarian M, Flavell RA, Wolin SL (2003) A Lupus-like Syndrome Develops in Mice Lacking the Ro 60 kDa Protein, a Major Lupus Autoantigen. Proc Natl Aca. Sci USA 100: 7503-7508.
[Featured in Editors' Choice: Highlights of the Recent Literature, Science 300: 1849-1850 (PDF); Research Notes, Nature Genetics 34: 250 (PDF)]
Wolin SL. and Cedervall T. (2002) The La protein. Ann Rev Biochem 71:375-403.
Long KS, Cedervall T, Walch-Solimena C, Noe DA, Huddleston MJ, Annan RS, Wolin SL. (2001) Phosphorylation of the S. cerevisiae La protein does not appear to be required for its functions in tRNA maturation and nascent RNA stabilization. RNA 7: 1589-1602.
Chen X, Quinn AM, Wolin SL. (2000) Ro ribonucleoproteins contribute to the resistance of Deinococcus radiodurans to ultraviolet irradiation. Genes Dev. 14: 777-782.
Xue D, Rubinson DA, Pannone BK, Yoo CJ, Wolin SL. (2000) U snRNP assembly in yeast involves the La protein. EMBO J. 19: 1650-1660.
