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Jonathan P. Staley

InstitutionUniversity of Chicago
DepartmentMolecular Genetics and Cell Biology
AddressChicago IL 60637
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    Collapse Overview 
    Collapse overview
    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 as well as human cells, 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, including in the context of transcription.

    Collapse Biography 
    Collapse education and training
    Haverford College, Haverford, PAB.A.1987Chemistry
    Massachusetts Institute of Technology (Advisor: Peter S. Kim), Boston, MAPh.D.1993Chemistry/Biophysics
    University of California at San Francisco (Advisor: Christine Guthrie), San Francisco, CAPostdoc1999Biochemistry/Genetics
    Collapse awards and honors
    2000 - 2001Young Investigator Award, Cancer Research Foundation
    2001 - 2006David & Lucile Packard Fellowship in Science and Engineering, Packard Foundation
    2006 - 2008Stephen F. Sener, M.D. - Research Scholar Award, American Cancer Society
    2014Distinguished Investigator Award, Biological Sciences Division, The University of Chicago
    2016Fellow, American Association for the Advancement of Science

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Fair B, Najar CBA, Zhao J, Lozano S, Reilly A, Mossian G, Staley JP, Wang J, Li YI. Global impact of aberrant splicing on human gene expression levels. bioRxiv. 2023 Oct 16. PMID: 37745605; PMCID: PMC10515962.
    2. Buerer L, Clark NE, Welch A, Duan C, Taggart AJ, Townley BA, Wang J, Soemedi R, Rong S, Lin CL, Zeng Y, Katolik A, Staley JP, Damha MJ, Mosammaparast N, Fairbrother WG. The debranching enzyme Dbr1 regulates lariat turnover and intron splicing. Res Sq. 2023 Jun 13. PMID: 37398028; PMCID: PMC10312976.
    3. Zeng Y, Fair BJ, Zeng H, Krishnamohan A, Hou Y, Hall JM, Ruthenburg AJ, Li YI, Staley JP. Profiling lariat intermediates reveals genetic determinants of early and late co-transcriptional splicing. Mol Cell. 2022 12 15; 82(24):4681-4699.e8. PMID: 36435176; PMCID: PMC10448999.
      Citations: 7     Fields:    Translation:HumansCells
    4. Toroney R, Nielsen KH, Staley JP. Termination of pre-mRNA splicing requires that the ATPase and RNA unwindase Prp43p acts on the catalytic snRNA U6. Genes Dev. 2019 11 01; 33(21-22):1555-1574. PMID: 31558568; PMCID: PMC6824469.
      Citations: 11     Fields:    Translation:Cells
    5. 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. PMID: 28416566; PMCID: PMC5473145.
      Citations: 27     Fields:    Translation:AnimalsCells
    6. 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. PMID: 27593161; PMCID: PMC5178103.
      Citations: 6     Fields:    Translation:Cells
    7. 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. PMID: 27528618; PMCID: PMC5064217.
      Citations: 27     Fields:    
    8. Piccirilli JA, Staley JP. Reverse transcriptases lend a hand in splicing catalysis. Nat Struct Mol Biol. 2016 06 07; 23(6):507-9. PMID: 27273636; PMCID: PMC6548540.
      Citations: 7     Fields:    Translation:Cells
    9. 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. PMID: 27034163; PMCID: PMC5041995.
      Citations: 88     Fields:    Translation:HumansAnimalsCells
    10. 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. PMID: 26919433; PMCID: PMC4979991.
      Citations: 78     Fields:    Translation:AnimalsCells
    11. 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. PMID: 26647463; PMCID: PMC4712674.
      Citations: 22     Fields:    Translation:AnimalsCells
    12. 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. PMID: 26137319; PMCID: PMC4469172.
      Citations: 4     
    13. 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. PMID: 24747940; PMCID: PMC4257784.
      Citations: 56     Fields:    Translation:AnimalsCells
    14. Tuttle N, Staley JP, Piccirilli JA, Li NS. 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. PMID: 24635216; PMCID: PMC4203407.
      Citations: 3     Fields:    Translation:Cells
    15. 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. PMID: 24442613; PMCID: PMC3923124.
      Citations: 26     Fields:    Translation:AnimalsCells
    16. 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. PMID: 24196718; PMCID: PMC4666680.
      Citations: 162     Fields:    Translation:AnimalsCells
    17. Koodathingal P, Staley JP. Splicing fidelity: DEAD/H-box ATPases as molecular clocks. RNA Biol. 2013 Jul; 10(7):1073-9. PMID: 23770752; PMCID: PMC3849154.
      Citations: 32     Fields:    Translation:Cells
    18. 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. PMID: 23686287; PMCID: PMC3703396.
      Citations: 24     Fields:    Translation:AnimalsCells
    19. 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. PMID: 23468430; PMCID: PMC3613610.
      Citations: 18     Fields:    Translation:AnimalsCells
    20. 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. PMID: 23154979; PMCID: PMC3505815.
      Citations: 6     Fields:    
    21. Semlow DR, Staley JP. Staying on message: ensuring fidelity in pre-mRNA splicing. Trends Biochem Sci. 2012 Jul; 37(7):263-73. PMID: 22564363; PMCID: PMC3735133.
      Citations: 61     Fields:    Translation:HumansAnimalsCells
    22. 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. PMID: 22539527; PMCID: PMC3358637.
      Citations: 15     Fields:    Translation:AnimalsCells
    23. 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. PMID: 20705241; PMCID: PMC3722364.
      Citations: 62     Fields:    Translation:AnimalsCells
    24. 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. PMID: 20463285; PMCID: PMC2890470.
      Citations: 59     Fields:    Translation:AnimalsCells
    25. 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. PMID: 19878916; PMCID: PMC2775825.
      Citations: 83     Fields:    Translation:HumansCells
    26. 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. PMID: 19458033; PMCID: PMC2704075.
      Citations: 51     Fields:    Translation:AnimalsCells
    27. Staley JP, Woolford JL. Assembly of ribosomes and spliceosomes: complex ribonucleoprotein machines. Curr Opin Cell Biol. 2009 Feb; 21(1):109-18. PMID: 19167202; PMCID: PMC2698946.
      Citations: 79     Fields:    Translation:HumansAnimalsCells
    28. Anderson AM, Staley JP. Long-distance splicing. Proc Natl Acad Sci U S A. 2008 May 13; 105(19):6793-4. PMID: 18474864; PMCID: PMC2383983.
      Citations: 1     Fields:    Translation:AnimalsCells
    29. 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. PMID: 18425143; PMCID: PMC2737727.
      Citations: 71     Fields:    Translation:AnimalsCells
    30. 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. PMID: 17403782; PMCID: PMC1838533.
      Citations: 65     Fields:    Translation:Cells
    31. Mayas RM, Staley JP. DEAD on. Nat Struct Mol Biol. 2006 Nov; 13(11):954-5. PMID: 17082789.
      Citations: 4     Fields:    Translation:AnimalsCells
    32. 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. PMID: 16885028; PMCID: PMC3777414.
      Citations: 106     Fields:    Translation:AnimalsCells
    33. 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. PMID: 16680161; PMCID: PMC3729281.
      Citations: 88     Fields:    Translation:Cells
    34. 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. PMID: 16382143; PMCID: PMC1346897.
      Citations: 73     Fields:    Translation:AnimalsCells
    35. Hilliker AK, Staley JP. Multiple functions for the invariant AGC triad of U6 snRNA. RNA. 2004 Jun; 10(6):921-8. PMID: 15146076; PMCID: PMC1370584.
      Citations: 42     Fields:    Translation:AnimalsCells
    36. Staley JP. Hanging on to the branch. Nat Struct Biol. 2002 Jan; 9(1):5-7. PMID: 11753425.
      Citations:    Fields:    Translation:Cells
    37. 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. PMID: 11172727.
      Citations: 92     Fields:    Translation:AnimalsCells
    38. 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. PMID: 10606479.
      Citations: 3     Fields:    Translation:Humans
    39. 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. PMID: 10024879.
      Citations: 159     Fields:    Translation:AnimalsCells
    40. Staley JP, Guthrie C. Mechanical devices of the spliceosome: motors, clocks, springs, and things. Cell. 1998 Feb 06; 92(3):315-26. PMID: 9476892.
      Citations: 512     Fields:    Translation:AnimalsCells
    41. 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. PMID: 7531529; PMCID: PMC2142600.
      Citations: 40     Fields:    Translation:AnimalsCells
    42. 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. PMID: 1371875; PMCID: PMC48483.
      Citations: 15     Fields:    Translation:Cells
    43. Staley JP, Kim PS. Role of a subdomain in the folding of bovine pancreatic trypsin inhibitor. Nature. 1990 Apr 12; 344(6267):685-8. PMID: 1691452.
      Citations: 14     Fields:    Translation:Cells
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