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
A retrovirus packages host noncoding RNAs from a novel surveillance pathway.
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.
Bacterial noncoding Y RNAs are widespread and mimic tRNAs
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.
An RNA degradation machine sculpted by Ro autoantigen and noncoding RNA.
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.
Nuclear noncoding RNA surveillance: is the end in sight?
Wolin, S.L., Sim, S. and Chen, X. (2012). Nuclear noncoding RNA surveillance: is the end in sight? Trends Genet. 28, 306-313.
The zipcode-binding protein ZBP1 influences the subcellular location of the Ro 60-kDa autoantigen and the noncoding Y3 RNA.
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.
An intrinsically disordered C-terminus allows the La protein to assist the biogenesis of diverse noncoding RNA precursors.
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.
Full List of PubMed Publications
- Wolin SL: Two for the price of one: RNA modification enzymes as chaperones. Proc Natl Acad Sci U S A. 2016 Dec 13; 2016 Nov 30. PMID: 27911836
- Telesnitsky A, Wolin SL: The Host RNAs in Retroviral Particles. Viruses. 2016 Aug 19; 2016 Aug 19. PMID: 27548206
- Eckwahl MJ, Arnion H, Kharytonchyk S, Zang T, Bieniasz PD, Telesnitsky A, Wolin SL: Analysis of the human immunodeficiency virus-1 RNA packageome. RNA. 2016 Aug; 2016 May 31. PMID: 27247436
- Eckwahl MJ, Telesnitsky A, Wolin SL: Host RNA Packaging by Retroviruses: A Newly Synthesized Story. MBio. 2016 Feb 9; 2016 Feb 9. PMID: 26861021
- Mount SM, Wolin SL: Recognizing the 35th anniversary of the proposal that snRNPs are involved in splicing. Mol Biol Cell. 2015 Oct 15. PMID: 26463979
- Eckwahl MJ, Sim S, Smith D, Telesnitsky A, Wolin SL: A retrovirus packages nascent host noncoding RNAs from a novel surveillance pathway. Genes Dev. 2015 Mar 15. PMID: 25792599
- Kosmaczewski SG, Edwards TJ, Han SM, Eckwahl MJ, Meyer BI, Peach S, Hesselberth JR, Wolin SL, Hammarlund M: The RtcB RNA ligase is an essential component of the metazoan unfolded protein response. EMBO Rep. 2014 Dec; 2014 Nov 3. PMID: 25366321
- Chen X, Sim S, Wurtmann EJ, Feke A, Wolin SL: Bacterial noncoding Y RNAs are widespread and mimic tRNAs. RNA. 2014 Nov; 2014 Sep 17. PMID: 25232022
- Wolin SL, Belair C, Boccitto M, Chen X, Sim S, Taylor DW, Wang HW: Non-coding Y RNAs as tethers and gates: Insights from bacteria. RNA Biol. 2013 Oct; 2013 Aug 22. PMID: 24036917
- Chen X, Taylor DW, Fowler CC, Galan JE, Wang HW, Wolin SL: An RNA degradation machine sculpted by Ro autoantigen and noncoding RNA. Cell. 2013 Mar 28. PMID: 23540697
- Wolin SL, Sim S, Chen X: Nuclear noncoding RNA surveillance: is the end in sight? Trends Genet. 2012 Jul; 2012 Apr 2. PMID: 22475369
- Rojas M, Farr GW, Fernandez CF, Lauden L, McCormack JC, Wolin SL: Yeast Gis2 and its human ortholog CNBP are novel components of stress-induced RNP granules. PLoS One. 2012; 2012 Dec 21. PMID: 23285195
- Sim S, Yao J, Weinberg DE, Niessen S, Yates JR 3rd, Wolin SL: The zipcode-binding protein ZBP1 influences the subcellular location of the Ro 60-kDa autoantigen and the noncoding Y3 RNA. RNA. 2012 Jan; 2011 Nov 23. PMID: 22114317
- Sim S, Wolin SL: Emerging roles for the Ro 60-kDa autoantigen in noncoding RNA metabolism. Wiley Interdiscip Rev RNA. 2011 Sep-Oct; 2011 Apr 21. PMID: 21823229
- Kucera NJ, Hodsdon ME, Wolin SL: An intrinsically disordered C terminus allows the La protein to assist the biogenesis of diverse noncoding RNA precursors. Proc Natl Acad Sci U S A. 2011 Jan 25; 2011 Jan 6. PMID: 21212361
- Hamill S, Wolin SL, Reinisch KM: Structure and function of the polymerase core of TRAMP, a RNA surveillance complex. Proc Natl Acad Sci U S A. 2010 Aug 24; 2010 Aug 9. PMID: 20696927
- Wurtmann EJ, Wolin SL: A role for a bacterial ortholog of the Ro autoantigen in starvation-induced rRNA degradation. Proc Natl Acad Sci U S A. 2010 Mar 2; 2010 Feb 16. PMID: 20160119
- Sim S, Weinberg DE, Fuchs G, Choi K, Chung J, Wolin SL: The subcellular distribution of an RNA quality control protein, the Ro autoantigen, is regulated by noncoding Y RNA binding. Mol Biol Cell. 2009 Mar; 2008 Dec 30. PMID: 19116308
- Wurtmann EJ, Wolin SL: RNA under attack: cellular handling of RNA damage. Crit Rev Biochem Mol Biol. 2009 Jan-Feb. PMID: 19089684
- Copela LA, Fernandez CF, Sherrer RL, Wolin SL: Competition between the Rex1 exonuclease and the La protein affects both Trf4p-mediated RNA quality control and pre-tRNA maturation. RNA. 2008 Jun; 2008 May 2. PMID: 18456844
- Chen X, Wurtmann EJ, Van Batavia J, Zybailov B, Washburn MP, Wolin SL: An ortholog of the Ro autoantigen functions in 23S rRNA maturation in D. radiodurans. Genes Dev. 2007 Jun 1; 2007 May 17. PMID: 17510283
- Reinisch KM, Wolin SL: Emerging themes in non-coding RNA quality control. Curr Opin Struct Biol. 2007 Apr; 2007 Mar 28. PMID: 17395456
- Fuchs G, Stein AJ, Fu C, Reinisch KM, Wolin SL: Structural and biochemical basis for misfolded RNA recognition by the Ro autoantigen. Nat Struct Mol Biol. 2006 Nov; 2006 Oct 15. PMID: 17041599
- Wolin SL, Reinisch KM: The Ro 60 kDa autoantigen comes into focus: interpreting epitope mapping experiments on the basis of structure. Autoimmun Rev. 2006 Jul; 2005 Nov 15. PMID: 16890888
- Copela LA, Chakshusmathi G, Sherrer RL, Wolin SL: The La protein functions redundantly with tRNA modification enzymes to ensure tRNA structural stability. RNA. 2006 Apr. PMID: 16581807
- Stein AJ, Fuchs G, Fu C, Wolin SL, Reinisch KM: Structural insights into RNA quality control: the Ro autoantigen binds misfolded RNAs via its central cavity. Cell. 2005 May 20. PMID: 15907467
- Fernandez CF, Pannone BK, Chen X, Fuchs G, Wolin SL: An Lsm2-Lsm7 complex in Saccharomyces cerevisiae associates with the small nucleolar RNA snR5. Mol Biol Cell. 2004 Jun; 2004 Apr 9. PMID: 15075370
- Chen X, Wolin SL: The Ro 60 kDa autoantigen: insights into cellular function and role in autoimmunity. J Mol Med (Berl). 2004 Apr. PMID: 15168680
- Dong G, Chakshusmathi G, Wolin SL, Reinisch KM: Structure of the La motif: a winged helix domain mediates RNA binding via a conserved aromatic patch. EMBO J. 2004 Mar 10; 2004 Feb 19. PMID: 14976553
- Chen X, Smith JD, Shi H, Yang DD, Flavell RA, Wolin SL: The Ro autoantigen binds misfolded U2 small nuclear RNAs and assists mammalian cell survival after UV irradiation. Curr Biol. 2003 Dec 16. PMID: 14680639
- Chakshusmathi G, Kim SD, Rubinson DA, Wolin SL: A La protein requirement for efficient pre-tRNA folding. EMBO J. 2003 Dec 15. PMID: 14657028
- Xue D, Shi H, Smith JD, Chen X, Noe DA, Cedervall T, Yang DD, Eynon E, Brash DE, Kashgarian M, Flavell RA, Wolin SL: A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen. Proc Natl Acad Sci U S A. 2003 Jun 24; 2003 Jun 3. PMID: 12788971
- Wolin SL, Cedervall T: The La protein. Annu Rev Biochem. 2002; 2001 Nov 9. PMID: 12045101