Jonathan P Staley
Research Summary / Selected Publications
Nuclear pre-mRNA splicing is ubiquitous in all eukaryotes and is required to excise introns before mRNA is translated by the ribosome. Further, splicing enables both a critical layer in the regulation of gene expression and a flexibility through alternative splicing that affords complexity in higher organisms, but splicing is also susceptible to mutations and underlies at least 15% of human diseases. Splicing is mediated by the spliceosome, a dynamic machine composed of both protein and noncoding RNA parts. Our lab investigates the role of these RNA components in substrate binding and catalysis, the mechanisms for proofreading splice site choice, the role for ATPases in dynamics and fidelity, and the regulation of splicing. Using budding yeast as a model system, we pursue these areas through a wide range of approaches, from single molecule microscopy and chemical biology to biochemistry, genetics, and genomics. CATALYSIS: Over three decades ago, the small nuclear RNA (snRNA) components of the spliceosome were proposed to mediate catalysis within the spliceosome. With the Piccirilli lab, we have provided definitive evidence that the spliceosome utilizes RNA to catalyze splicing. This work has raised new questions regarding the mechanism...
Fica SM†, Mefford MA†, Piccirilli JA & Staley JP. Evidence for formation of a catalytic triplex in the spliceosome. Nature Structural and Molecular Biology, 21:464-71. †Co-first authors. NSMB
Wlodaver A & Staley JP. (2014) The DExD/H-box ATPase Prp2 destabilizes and proofreads the catalytic RNA core of the spliceosome, RNA, 20:282-94. RNA
Fica SM†, Tuttle N†, Novak N, Li N-L, Lu J, Koodathingal P, Dai Q, Staley JP*, and Piccirilli JA*. (2013) RNA catalyzes nuclear pre-mRNA splicing, Nature, 503:229-34. †Co-first authors; *Co-corresponding authors; see Nature website for accompanying News & Views, "Metal ghosts in the splicing machine". Nature
Koodathingal P & Staley JP. (2013) Splicing fidelity: DExD/H-box ATPases as molecular clocks. RNA Biology, 10:1073-1079. RNA Biology
Kannan R, Hartnett S, Voelker RB, Berglund JA, Staley JP & Baumann P. (2013) Intronic sequence elements impede exon ligation and trigger a discard pathway that yields functional telomerase RNA in fission yeast. Genes and Development, 27:627-38. Genes & Development