- RNA helicases
We investigate roles and functions of RNA helicases, enzymes that use ATP to bind or remodel RNA and RNA-protein complexes. RNA helicases are the largest class of enzymes in eukaryotic RNA metabolism. The proteins are structurally highly conserved and involved in virtually all aspects of RNA metabolism from bacteria to humans. Wherever there is RNA in the cell, an RNA helicase is probably there, too. Deregulation or malfunction of certain RNA helicases has been linked to numerous diseases, from neurological disorders, to cancer and infectious disease.
Despite their central biological roles, it is not well understood what RNA helicases actually do in the cell. It has become clear that the name “helicase” does not imply that these enzymes just unwind RNA duplexes, but it has remained enigmatic what reactions they catalyze. Another puzzling issue is the apparent contradiction between promiscuous action of RNA helicases in vitro – they will unwind or bind to essentially any RNA – and their specificity in the cell – RNA helicases can usually not substitute for one another, despite their high level structural similarity.
Our goal is to understand how RNA helicases physically function in isolation and in the cell. We approach this aim from two sides – by analyzing the enzymatic properties of prototypical RNA helicases in isolation and by determining how these proteins then function in their biological environment. We utilize techniques ranging from molecular biology approaches on yeast along with deep sequencing (RNA-seq) to quantitative biochemical and biophysical methods, including single molecule fluorescence.
Since RNA helicases play central biological roles, our studies have broad implications for understanding the regulation of gene expression, to delineating the cellular response to viral infections.
Jia H, Yang X, Anderson JT & Jankowsky E: "RNA unwinding by the Trf4/Air2/Mtr4 Polyadenylation (TRAMP) complex." Proc. Natl. Acad. Sci. USA 109, 7292-7297 (2012)
Jia H, Wang X, Liu F, Guenther UP, Srinivasan S, Anderson JT & Jankowsky E: “The RNA helicase Mtr4p modulates polyadenylation in the TRAMP complex.” Cell 145, 890-901 (2011)
Liu F, Putnam A & Jankowsky E “ATP hydrolysis is required for DEAD-box protein recycling but not for duplex unwinding.” Proc. Natl. Acad. Sci. USA 105, 20209-20214 (2008)
Yang Q, Del Campo M, Lambowitz AM & Jankowsky E “DEAD-box proteins unwind duplexes by local strand separation” Molecular Cell 28, 253-264 (2007)
Fairman ME, Maroney P, Wang W, Bowers H, Gollnick P, Nilsen, TW & Jankowsky E “Protein displacement by DExH/D ‘RNA helicases’ without duplex unwinding.” Science 304, 730-734 (2004)