Jonathan P. Staley

Research Summary
Our goal is to understand the mechanism and regulation of nuclear pre-mRNA splicing, an essential step in eukaryotic gene expression. Pre-mRNA splicing is catalyzed by a massive multimegadalton ribonucleoprotein machine called the spliceosome. Using the model organism S. cerevisiae, we apply a wide array of approaches, ranging from single molecule microscopy, biophysics, and chemical biology to biochemistry and cell biology to genetics and genomics to gain a deep understanding of how the spliceosome catalyzes and regulates pre-mRNA splicing.
Keywords
splicing, RNA, Messenger RNA, RNA Sequence, Spliceosome, Intron, Pre-mRNA, ATPase, RNA dependent ATPase, RNA Helicase, DEAD-box RNA Helicases, Gene Expression Regulation, Baker's Yeast, Brewer's Yeast, Yeast Proteins, Exon, Nuclear Export, snRNA, DEAH-box RNA helicase
Education
  • Haverford College, Haverford, PA, B.A. Chemistry 1987
  • Massachusetts Institute of Technology (Advisor: Peter S. Kim), Boston, MA, Ph.D. Chemistry/Biophysics 1993
  • University of California at San Francisco, San Francisco, CA, Postdoc Biochemistry/Genetics 1999
Biosciences Graduate Program Association
Awards & Honors
  • 2000 - 2001 Young Investigator Award Cancer Research Foundation
  • 2001 - 2006 David & Lucile Packard Fellowship in Science and Engineering Packard Foundation
  • 2006 - 2008 Stephen F. Sener, M.D. - Research Scholar Award American Cancer Society
  • 2014 - Distinguished Investigator Award, Biological Sciences Division The University of Chicago
  • 2016 - Fellow American Association for the Advancement of Science
Publications
  1. He Y, Staley JP, Andersen GR, Nielsen KH. Structure of the DEAH/RHA ATPase Prp43p bound to RNA implicates a pair of hairpins and motif Va in translocation along RNA. RNA. 2017 07; 23(7):1110-1124. View in: PubMed

  2. Shao Y, Huang H, Qin D, Li NS, Koide A, Staley JP, Koide S, Kossiakoff AA, Piccirilli JA. Specific Recognition of a Single-Stranded RNA Sequence by a Synthetic Antibody Fragment. J Mol Biol. 2016 10 09; 428(20):4100-4114. View in: PubMed

  3. Soucek S, Zeng Y, Bellur DL, Bergkessel M, Morris KJ, Deng Q, Duong D, Seyfried NT, Guthrie C, Staley JP, Fasken MB, Corbett AH. The Evolutionarily-conserved Polyadenosine RNA Binding Protein, Nab2, Cooperates with Splicing Machinery to Regulate the Fate of pre-mRNA. Mol Cell Biol. 2016 11; 36(21):2697-2714. View in: PubMed

  4. Piccirilli JA, Staley JP. Reverse transcriptases lend a hand in splicing catalysis. Nat Struct Mol Biol. 2016 06 07; 23(6):507-9. View in: PubMed

  5. Ranoa DR, Parekh AD, Pitroda SP, Huang X, Darga T, Wong AC, Huang L, Andrade J, Staley JP, Satoh T, Akira S, Weichselbaum RR, Khodarev NN. Cancer therapies activate RIG-I-like receptor pathway through endogenous non-coding RNAs. Oncotarget. 2016 May 03; 7(18):26496-515. View in: PubMed

  6. Semlow DR, Blanco MR, Walter NG, Staley JP. Spliceosomal DEAH-Box ATPases Remodel Pre-mRNA to Activate Alternative Splice Sites. Cell. 2016 Feb 25; 164(5):985-98. View in: PubMed

  7. Qin D, Huang L, Wlodaver A, Andrade J, Staley JP. Sequencing of lariat termini in S. cerevisiae reveals 5' splice sites, branch points, and novel splicing events. RNA. 2016 Feb; 22(2):237-53. View in: PubMed

  8. Liu Y, Chen X, Qin B, Zhao K, Zhao Q, Staley JP, Zhao C. Knocking Down Snrnp200 Initiates Demorphogenesis of Rod Photoreceptors in Zebrafish. J Ophthalmol. 2015; 2015:816329. View in: PubMed

  9. Fica SM, Mefford MA, Piccirilli JA, Staley JP. Evidence for a group II intron-like catalytic triplex in the spliceosome. Nat Struct Mol Biol. 2014 May; 21(5):464-471. View in: PubMed

  10. Li NS, Tuttle N, Staley JP, Piccirilli JA. Synthesis and incorporation of the phosphoramidite derivative of 2'-O-photocaged 3'-s-thioguanosine into oligoribonucleotides: substrate for probing the mechanism of RNA catalysis. J Org Chem. 2014 Apr 18; 79(8):3647-52. View in: PubMed

  11. Wlodaver AM, Staley JP. The DExD/H-box ATPase Prp2p destabilizes and proofreads the catalytic RNA core of the spliceosome. RNA. 2014 Mar; 20(3):282-94. View in: PubMed

  12. Fica SM, Tuttle N, Novak T, Li NS, Lu J, Koodathingal P, Dai Q, Staley JP, Piccirilli JA. RNA catalyses nuclear pre-mRNA splicing. Nature. 2013 Nov 14; 503(7475):229-34. View in: PubMed

  13. Koodathingal P, Staley JP. Splicing fidelity: DEAD/H-box ATPases as molecular clocks. RNA Biol. 2013 Jul; 10(7):1073-9. View in: PubMed

  14. Schellenberg MJ, Wu T, Ritchie DB, Fica S, Staley JP, Atta KA, LaPointe P, MacMillan AM. A conformational switch in PRP8 mediates metal ion coordination that promotes pre-mRNA exon ligation. Nat Struct Mol Biol. 2013 Jun; 20(6):728-34. View in: PubMed

  15. Kannan R, Hartnett S, Voelker RB, Berglund JA, Staley JP, Baumann P. Intronic sequence elements impede exon ligation and trigger a discard pathway that yields functional telomerase RNA in fission yeast. Genes Dev. 2013 Mar 15; 27(6):627-38. View in: PubMed

  16. Nielsen KH, Staley JP. Spliceosome activation: U4 is the path, stem I is the goal, and Prp8 is the keeper. Let's cheer for the ATPase Brr2! Genes Dev. 2012 Nov 15; 26(22):2461-7. View in: PubMed

  17. Semlow DR, Staley JP. Staying on message: ensuring fidelity in pre-mRNA splicing. Trends Biochem Sci. 2012 Jul; 37(7):263-73. View in: PubMed

  18. Kim Guisbert KS, Zhang Y, Flatow J, Hurtado S, Staley JP, Lin S, Sontheimer EJ. Meiosis-induced alterations in transcript architecture and noncoding RNA expression in S. cerevisiae. RNA. 2012 Jun; 18(6):1142-53. View in: PubMed

  19. Koodathingal P, Novak T, Piccirilli JA, Staley JP. The DEAH box ATPases Prp16 and Prp43 cooperate to proofread 5' splice site cleavage during pre-mRNA splicing. Mol Cell. 2010 Aug 13; 39(3):385-95. View in: PubMed

  20. Mayas RM, Maita H, Semlow DR, Staley JP. Spliceosome discards intermediates via the DEAH box ATPase Prp43p. Proc Natl Acad Sci U S A. 2010 Jun 01; 107(22):10020-5. View in: PubMed

  21. Zhao C, Bellur DL, Lu S, Zhao F, Grassi MA, Bowne SJ, Sullivan LS, Daiger SP, Chen LJ, Pang CP, Zhao K, Staley JP, Larsson C. Autosomal-dominant retinitis pigmentosa caused by a mutation in SNRNP200, a gene required for unwinding of U4/U6 snRNAs. Am J Hum Genet. 2009 Nov; 85(5):617-27. View in: PubMed

  22. Mefford MA, Staley JP. Evidence that U2/U6 helix I promotes both catalytic steps of pre-mRNA splicing and rearranges in between these steps. RNA. 2009 Jul; 15(7):1386-97. View in: PubMed

  23. Staley JP, Woolford JL. Assembly of ribosomes and spliceosomes: complex ribonucleoprotein machines. Curr Opin Cell Biol. 2009 Feb; 21(1):109-18. View in: PubMed

  24. Anderson AM, Staley JP. Long-distance splicing. Proc Natl Acad Sci U S A. 2008 May 13; 105(19):6793-4. View in: PubMed

  25. Bellare P, Small EC, Huang X, Wohlschlegel JA, Staley JP, Sontheimer EJ. A role for ubiquitin in the spliceosome assembly pathway. Nat Struct Mol Biol. 2008 May; 15(5):444-51. View in: PubMed

  26. Hilliker AK, Mefford MA, Staley JP. U2 toggles iteratively between the stem IIa and stem IIc conformations to promote pre-mRNA splicing. Genes Dev. 2007 Apr 01; 21(7):821-34. View in: PubMed

  27. Mayas RM, Staley JP. DEAD on. Nat Struct Mol Biol. 2006 Nov; 13(11):954-5. View in: PubMed

  28. Small EC, Leggett SR, Winans AA, Staley JP. The EF-G-like GTPase Snu114p regulates spliceosome dynamics mediated by Brr2p, a DExD/H box ATPase. Mol Cell. 2006 Aug 04; 23(3):389-99. View in: PubMed

  29. Mayas RM, Maita H, Staley JP. Exon ligation is proofread by the DExD/H-box ATPase Prp22p. Nat Struct Mol Biol. 2006 Jun; 13(6):482-90. View in: PubMed

  30. Leeds NB, Small EC, Hiley SL, Hughes TR, Staley JP. The splicing factor Prp43p, a DEAH box ATPase, functions in ribosome biogenesis. Mol Cell Biol. 2006 Jan; 26(2):513-22. View in: PubMed

  31. Hilliker AK, Staley JP. Multiple functions for the invariant AGC triad of U6 snRNA. RNA. 2004 Jun; 10(6):921-8. View in: PubMed

  32. Staley JP. Hanging on to the branch. Nat Struct Biol. 2002 Jan; 9(1):5-7. View in: PubMed

  33. Chen JY, Stands L, Staley JP, Jackups RR, Latus LJ, Chang TH. Specific alterations of U1-C protein or U1 small nuclear RNA can eliminate the requirement of Prp28p, an essential DEAD box splicing factor. Mol Cell. 2001 Jan; 7(1):227-32. View in: PubMed

  34. Blank KR, Whittington R, Arjomandy B, Wein AJ, Broderick G, Staley J, Malkowicz SB. Neoadjuvant androgen deprivation prior to transperineal prostate brachytherapy: smaller volumes, less morbidity. Cancer J Sci Am. 1999 Nov-Dec; 5(6):370-3. View in: PubMed

  35. Staley JP, Guthrie C. An RNA switch at the 5' splice site requires ATP and the DEAD box protein Prp28p. Mol Cell. 1999 Jan; 3(1):55-64. View in: PubMed

  36. Staley JP, Guthrie C. Mechanical devices of the spliceosome: motors, clocks, springs, and things. Cell. 1998 Feb 06; 92(3):315-26. View in: PubMed

  37. Staley JP, Kim PS. Formation of a native-like subdomain in a partially folded intermediate of bovine pancreatic trypsin inhibitor. Protein Sci. 1994 Oct; 3(10):1822-32. View in: PubMed

  38. Staley JP, Kim PS. Role of a subdomain in the folding of bovine pancreatic trypsin inhibitor. Nature. 1990 Apr 12; 344(6267):685-8. View in: PubMed

  39. Staley JP, Kim PS. Complete folding of bovine pancreatic trypsin inhibitor with only a single disulfide bond. Proc Natl Acad Sci U S A. 1992 Mar 01; 89(5):1519-23. View in: PubMed