Sandra Wolin, MD, PhD
Research & Publications
Biography
News
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.
Specialized Terms: Noncoding RNAs; RNA surveillance; RNA damage; Autoimmune disease; Environmental stress
Coauthors
Selected Publications
- Bacterial Y RNAs: Gates, Tethers, and tRNA MimicsSim S, Wolin S. Bacterial Y RNAs: Gates, Tethers, and tRNA Mimics. 2018, 369-381. DOI: 10.1128/9781683670247.ch21.
- 084 The role of interferon and retroelements in lupus-prone Ro60 knockout mouse skinRokunohe D, Chiou E, Sun X, Tanaka L, Wolin S, Elkon K, Kawasumi M. 084 The role of interferon and retroelements in lupus-prone Ro60 knockout mouse skin. Journal Of Investigative Dermatology 2018, 138: s14. DOI: 10.1016/j.jid.2018.03.088.
- 068 Lupus Ro60 autoantigen cross-reactivity with commensal Ro60 orthologsGreiling T, Dehner C, Chen X, Hughes K, Vieira S, Ruff W, Sim S, Wolin S, Kriegel M. 068 Lupus Ro60 autoantigen cross-reactivity with commensal Ro60 orthologs. Journal Of Investigative Dermatology 2017, 137: s12. DOI: 10.1016/j.jid.2017.02.081.
- 234 Anti-Ro60 T and B cells in human lupus cross-react with Ro60 orthologs from cutaneous commensalsGreiling T, Dehner C, Renfroe S, Chen X, Vieira S, Ruff W, Girardi M, Goodman A, Wolin S, Kriegel M. 234 Anti-Ro60 T and B cells in human lupus cross-react with Ro60 orthologs from cutaneous commensals. Journal Of Investigative Dermatology 2016, 136: s42. DOI: 10.1016/j.jid.2016.02.263.
- A retrovirus packages nascent host noncoding RNAs from a novel surveillance pathwayEckwahl MJ, Sim S, Smith D, Telesnitsky A, Wolin SL. A retrovirus packages nascent host noncoding RNAs from a novel surveillance pathway. Genes & Development 2015, 29: 646-657. PMID: 25792599, PMCID: PMC4378196, DOI: 10.1101/gad.258731.115.
- Bacterial noncoding Y RNAs are widespread and mimic tRNAsChen X, Sim S, Wurtmann EJ, Feke A, Wolin SL. Bacterial noncoding Y RNAs are widespread and mimic tRNAs. RNA 2014, 20: 1715-1724. PMID: 25232022, PMCID: PMC4201824, DOI: 10.1261/rna.047241.114.
- An RNA Degradation Machine Sculpted by Ro Autoantigen and Noncoding RNAChen X, Taylor DW, Fowler CC, Galan JE, Wang HW, Wolin SL. An RNA Degradation Machine Sculpted by Ro Autoantigen and Noncoding RNA. Cell 2013, 153: 166-177. PMID: 23540697, PMCID: PMC3646564, DOI: 10.1016/j.cell.2013.02.037.
- An MBoC Favorite: The historic covers selected by Joseph Gall that graced MBoC from 1992 to 1996Wolin S. An MBoC Favorite: The historic covers selected by Joseph Gall that graced MBoC from 1992 to 1996. Molecular Biology Of The Cell 2012, 23: 1797-1797. PMCID: PMC3350544, DOI: 10.1091/mbc.e12-02-0141.
- Nuclear noncoding RNA surveillance: is the end in sight?Wolin SL, Sim S, Chen X. Nuclear noncoding RNA surveillance: is the end in sight? Trends In Genetics 2012, 28: 306-313. PMID: 22475369, PMCID: PMC3378728, DOI: 10.1016/j.tig.2012.03.005.
- The zipcode-binding protein ZBP1 influences the subcellular location of the Ro 60-kDa autoantigen and the noncoding Y3 RNASim S, Yao J, Weinberg DE, Niessen S, Yates JR, Wolin SL. The zipcode-binding protein ZBP1 influences the subcellular location of the Ro 60-kDa autoantigen and the noncoding Y3 RNA. RNA 2011, 18: 100-110. PMID: 22114317, PMCID: PMC3261732, DOI: 10.1261/rna.029207.111.
- An intrinsically disordered C terminus allows the La protein to assist the biogenesis of diverse noncoding RNA precursorsKucera NJ, Hodsdon ME, Wolin SL. An intrinsically disordered C terminus allows the La protein to assist the biogenesis of diverse noncoding RNA precursors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 1308-1313. PMID: 21212361, PMCID: PMC3029687, DOI: 10.1073/pnas.1017085108.
- Running Rings Around RNA: The role of Ro RNPs in RNA maturation and decayWolin S. Running Rings Around RNA: The role of Ro RNPs in RNA maturation and decay. The FASEB Journal 2008, 22: 527.3-527.3. DOI: 10.1096/fasebj.22.1_supplement.527.3.
- Molecular Chaperones and Quality Control in Noncoding RNA BiogenesisWOLIN S, WURTMANN E. Molecular Chaperones and Quality Control in Noncoding RNA Biogenesis. Cold Spring Harbor Symposia On Quantitative Biology 2006, 71: 505-511. PMID: 17381333, DOI: 10.1101/sqb.2006.71.051.
- Phosphorylation of the Saccharomyces cerevisiae La protein does not appear to be required for its functions in tRNA maturation and nascent RNA stabilization.Long K, Cedervall T, Walch-Solimena C, Noe D, Huddleston M, Annan R, Wolin S. Phosphorylation of the Saccharomyces cerevisiae La protein does not appear to be required for its functions in tRNA maturation and nascent RNA stabilization. RNA 2001, 7: 1589-602. PMID: 11720288, PMCID: PMC1370201.
- Multiple Functional Interactions Between Components of the Lsm2-Lsm8 Complex, U6 snRNA, and the Yeast La ProteinPannone B, Do Kim S, Noe D, Wolin S. Multiple Functional Interactions Between Components of the Lsm2-Lsm8 Complex, U6 snRNA, and the Yeast La Protein. Genetics 2001, 158: 187-196. PMID: 11333229, PMCID: PMC1461625, DOI: 10.1093/genetics/158.1.187.
- U snRNP assembly in yeast involves the La proteinXue D, Rubinson D, Pannone B, Yoo C, Wolin S. U snRNP assembly in yeast involves the La protein. The EMBO Journal 2000, 19: 2763-2763. DOI: 10.1093/emboj/19.11.2763.
- RNA degradation: Sm-like proteins wRING the neck of mRNAPannone B, Wolin S. RNA degradation: Sm-like proteins wRING the neck of mRNA. Current Biology 2000, 10: r478-r481. PMID: 10898971, DOI: 10.1016/s0960-9822(00)00552-2.
- U snRNP assembly in yeast involves the La proteinXue D, Rubinson D, Pannone B, Yoo C, Wolin S. U snRNP assembly in yeast involves the La protein. The EMBO Journal 2000, 19: 1650-1660. PMID: 10747032, PMCID: PMC310233, DOI: 10.1093/emboj/19.7.1650.
- Ro ribonucleoproteins contribute to the resistance of Deinococcus radiodurans to ultraviolet irradiationChen X, Quinn A, Wolin S. Ro ribonucleoproteins contribute to the resistance of Deinococcus radiodurans to ultraviolet irradiation. Genes & Development 2000, 14: 777-782. PMID: 10766734, PMCID: PMC316496, DOI: 10.1101/gad.14.7.777.
- Import of proteins into the trypanosome nucleus and their distribution at karyokinesisMarchetti M, Tschudi C, Kwon H, Wolin S, Ullu E. Import of proteins into the trypanosome nucleus and their distribution at karyokinesis. Journal Of Cell Science 2000, 113: 899-906. PMID: 10671379, DOI: 10.1242/jcs.113.5.899.
- erratum: Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particleSeto A, Zaug A, Sobel S, Wolin S, Cech T. erratum: Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particle. Nature 1999, 402: 898-898. DOI: 10.1038/47284.
- Two Yeast La Motif-containing Proteins Are RNA-binding Proteins that Associate with PolyribosomesSobel S, Wolin S. Two Yeast La Motif-containing Proteins Are RNA-binding Proteins that Associate with Polyribosomes. Molecular Biology Of The Cell 1999, 10: 3849-3862. PMID: 10564276, PMCID: PMC25684, DOI: 10.1091/mbc.10.11.3849.
- Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particleSeto A, Zaug A, Sobel S, Wolin S, Cech T. Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particle. Nature 1999, 401: 177-180. PMID: 10490028, DOI: 10.1038/43694.
- The trials and travels of tRNAWolin S, Matera A. The trials and travels of tRNA. Genes & Development 1999, 13: 1-10. PMID: 9887094, DOI: 10.1101/gad.13.1.1.
- A role for the yeast La protein in U6 snRNP assembly: evidence that the La protein is a molecular chaperone for RNA polymerase III transcriptsPannone B, Xue D, Wolin S. A role for the yeast La protein in U6 snRNP assembly: evidence that the La protein is a molecular chaperone for RNA polymerase III transcripts. The EMBO Journal 1998, 17: 7442-7453. PMID: 9857199, PMCID: PMC1171088, DOI: 10.1093/emboj/17.24.7442.
- Analyses of Ribosome Distribution During In Vitro TranslationWolin S. Analyses of Ribosome Distribution During In Vitro Translation. 1998, 77: 1-9. PMID: 9770657, DOI: 10.1385/0-89603-397-x:1.
- Binding of the 60-kDa Ro autoantigen to Y RNAs: evidence for recognition in the major groove of a conserved helix.Green C, Long K, Shi H, Wolin S. Binding of the 60-kDa Ro autoantigen to Y RNAs: evidence for recognition in the major groove of a conserved helix. RNA 1998, 4: 750-65. PMID: 9671049, PMCID: PMC1369656, DOI: 10.1017/s1355838298971667.
- The La protein in Schizosaccharomyces pombe: a conserved yet dispensable phosphoprotein that functions in tRNA maturation.Van Horn D, Yoo C, Xue D, Shi H, Wolin S. The La protein in Schizosaccharomyces pombe: a conserved yet dispensable phosphoprotein that functions in tRNA maturation. RNA 1997, 3: 1434-43. PMID: 9404894, PMCID: PMC1369584.
- The Yeast La Protein Is Required for the 3′ Endonucleolytic Cleavage That Matures tRNA PrecursorsYoo C, Wolin S. The Yeast La Protein Is Required for the 3′ Endonucleolytic Cleavage That Matures tRNA Precursors. Cell 1997, 89: 393-402. PMID: 9150139, DOI: 10.1016/s0092-8674(00)80220-2.
- A misfolded form of 5S rRNA is complexed with the Ro and La autoantigens.Shi H, O'Brien C, Van Horn D, Wolin S. A misfolded form of 5S rRNA is complexed with the Ro and La autoantigens. RNA 1996, 2: 769-84. PMID: 8752087, PMCID: PMC1369414.
- A perinucleolar compartment contains several RNA polymerase III transcripts as well as the polypyrimidine tract-binding protein, hnRNP I.Matera A, Frey M, Margelot K, Wolin S. A perinucleolar compartment contains several RNA polymerase III transcripts as well as the polypyrimidine tract-binding protein, hnRNP I. Journal Of Cell Biology 1995, 129: 1181-1193. PMID: 7539809, PMCID: PMC2120477, DOI: 10.1083/jcb.129.5.1181.
- Caenorhabditis elegans embryos contain only one major species of Ro RNP.Van Horn D, Eisenberg D, O'Brien C, Wolin S. Caenorhabditis elegans embryos contain only one major species of Ro RNP. RNA 1995, 1: 293-303. PMID: 7489501, PMCID: PMC1369082.
- A possible role for the 60-kD Ro autoantigen in a discard pathway for defective 5S rRNA precursors.O'Brien C, Wolin S. A possible role for the 60-kD Ro autoantigen in a discard pathway for defective 5S rRNA precursors. Genes & Development 1994, 8: 2891-2903. PMID: 7995526, DOI: 10.1101/gad.8.23.2891.
- La Proteins from Drosophila melanogaster and Saccharomyces cerevisiae: a Yeast Homolog of the La Autoantigen Is Dispensable for GrowthYoo C, Wolin S. La Proteins from Drosophila melanogaster and Saccharomyces cerevisiae: a Yeast Homolog of the La Autoantigen Is Dispensable for Growth. Molecular And Cellular Biology 1994, 14: 5412-5424. DOI: 10.1128/mcb.14.8.5412-5424.1994.
- La proteins from Drosophila melanogaster and Saccharomyces cerevisiae: a yeast homolog of the La autoantigen is dispensable for growth.Yoo C, Wolin S. La proteins from Drosophila melanogaster and Saccharomyces cerevisiae: a yeast homolog of the La autoantigen is dispensable for growth. Molecular And Cellular Biology 1994, 14: 5412-5424. PMID: 8035818, PMCID: PMC359060, DOI: 10.1128/mcb.14.8.5412.
- From the elephant to E. coli: SRP-dependent protein targetingWolin S. From the elephant to E. coli: SRP-dependent protein targeting. Cell 1994, 77: 787-790. PMID: 8004667, DOI: 10.1016/0092-8674(94)90124-4.
- Xenopus Ro ribonucleoproteins: members of an evolutionarily conserved class of cytoplasmic ribonucleoproteins.O'Brien C, Margelot K, Wolin S. Xenopus Ro ribonucleoproteins: members of an evolutionarily conserved class of cytoplasmic ribonucleoproteins. Proceedings Of The National Academy Of Sciences Of The United States Of America 1993, 90: 7250-7254. PMID: 7688474, PMCID: PMC47114, DOI: 10.1073/pnas.90.15.7250.
- Discrete nascent chain lengths are required for the insertion of presecretory proteins into microsomal membranes.Wolin S, Walter P. Discrete nascent chain lengths are required for the insertion of presecretory proteins into microsomal membranes. Journal Of Cell Biology 1993, 121: 1211-1219. PMID: 8389768, PMCID: PMC2119713, DOI: 10.1083/jcb.121.6.1211.
- Small ribonucleoproteinsWolin S, Walter P. Small ribonucleoproteins. Current Opinion In Structural Biology 1991, 1: 251-257. DOI: 10.1016/0959-440x(91)90070-a.
- Signal recognition particle mediates a transient elongation arrest of preprolactin in reticulocyte lysate.Wolin S, Walter P. Signal recognition particle mediates a transient elongation arrest of preprolactin in reticulocyte lysate. Journal Of Cell Biology 1989, 109: 2617-2622. PMID: 2556403, PMCID: PMC2115964, DOI: 10.1083/jcb.109.6.2617.
- Ribosome pausing and stacking during translation of a eukaryotic mRNA.Wolin S, Walter P. Ribosome pausing and stacking during translation of a eukaryotic mRNA. The EMBO Journal 1988, 7: 3559-3569. PMID: 2850168, PMCID: PMC454858, DOI: 10.1002/j.1460-2075.1988.tb03233.x.
- A new lamin in Xenopus somatic tissues displays strong homology to human lamin A.Wolin S, Krohne G, Kirschner M. A new lamin in Xenopus somatic tissues displays strong homology to human lamin A. The EMBO Journal 1987, 6: 3809-18. PMID: 3428277, PMCID: PMC553853, DOI: 10.1002/j.1460-2075.1987.tb02717.x.
- Nuclear lamin LI of Xenopus laevis: cDNA cloning, amino acid sequence and binding specificity of a member of the lamin B subfamily.Krohne G, Wolin S, McKeon F, Franke W, Kirschner M. Nuclear lamin LI of Xenopus laevis: cDNA cloning, amino acid sequence and binding specificity of a member of the lamin B subfamily. The EMBO Journal 1987, 6: 3801-8. PMID: 3428276, PMCID: PMC553852, DOI: 10.1002/j.1460-2075.1987.tb02716.x.
- A Subset of Yeast snRNA's Contains Functional Binding Sites for the Highly Conserved Sm AntigenRiedel N, Wolin S, Guthrie C. A Subset of Yeast snRNA's Contains Functional Binding Sites for the Highly Conserved Sm Antigen. Science 1987, 235: 328-331. PMID: 2948278, DOI: 10.1126/science.2948278.
- Small cytoplasmic ribonucleoproteinsWolin S. Small cytoplasmic ribonucleoproteins. Trends In Genetics 1985, 1: 201-204. DOI: 10.1016/0168-9525(85)90080-0.
- Genes for two small cytoplasmic Ro RNAs are adjacent and appear to be single-copy in the human genomeWolin S, Steitz J. Genes for two small cytoplasmic Ro RNAs are adjacent and appear to be single-copy in the human genome. Cell 1983, 32: 735-744. PMID: 6187471, DOI: 10.1016/0092-8674(83)90059-4.
- Structure and Function of Small Ribonucleoproteins from Eukaryotic CellsSteitz JA, Berg C, Gottlieb E, Hardin JA, Hashimoto C, Hendrick JP, Hinterberger M, Krikeles M, Lerner MR, Mount SM, Pettersson I, Rinke J, Rosa M, Wolin S. Structure and Function of Small Ribonucleoproteins from Eukaryotic Cells. 1983, 12: 309-317. PMID: 7166547, DOI: 10.1016/b978-0-12-501650-6.50023-7.
- Small RNPs in eucaryotic cellsHendrick J, Mount S, Rinke J, Wolin S, Rosa M, Gottlieb E, Lerner M, Steitz J. Small RNPs in eucaryotic cells. 1982, 321-328. DOI: 10.1007/978-1-349-06343-7_44.
- Ro Small Cytoplasmic Ribonucleoproteins Are a Subclass of La Ribonucleoproteins: Further Characterization of the Ro and La Small Ribonucleoproteins from Uninfected Mammalian CellsHendrick J, Wolin S, Rinke J, Lerner M, Steitz J. Ro Small Cytoplasmic Ribonucleoproteins Are a Subclass of La Ribonucleoproteins: Further Characterization of the Ro and La Small Ribonucleoproteins from Uninfected Mammalian Cells. Molecular And Cellular Biology 1981, 1: 1138-1149. DOI: 10.1128/mcb.1.12.1138-1149.1981.
- Are snRNPs involved in splicing?Lerner M, Boyle J, Mount S, Wolin S, Steitz J. Are snRNPs involved in splicing? Nature 1980, 283: 220-224. PMID: 7350545, DOI: 10.1038/283220a0.
- Expression of microtubule networks in normal cells, transformed cells, and their hybrids.Wolin S, Kucherlapati R. Expression of microtubule networks in normal cells, transformed cells, and their hybrids. Journal Of Cell Biology 1979, 82: 76-85. PMID: 383725, PMCID: PMC2110424, DOI: 10.1083/jcb.82.1.76.