ChE Seminar – “Speed-dating for small RNAs with the Hfq chaperone” by Dr. Sarah Woodson (Johns Hopkins University)

Host: Drs. Lydia Contreras and Hal Alper; Cockrell School Endowed Lectureship

ABSTRACT: 

Small non-coding RNAs (sRNAs) regulate gene expression post-transcription in response to stress and other environmental signals. sRNAs contribute to bacterial pathogenesis and environmental adaptation. sRNA regulation requires the protein Hfq, which chaperones base pairing between sRNAs and their target mRNAs.  Hfq binds sRNAs and their mRNA targets, and accelerates base pairing between complementary sequences in the two RNAs. Time-resolved FRET experiments and light-triggered base pairing show that a patch of arginines on Hfq protein are needed for its chaperone activity. Like many RNA binding proteins, Hfq proteins possess flexible, unstructured extensions whose functions are poorly understood. We showed that acidic residues at the C-terminus of E. coli Hfq mimic nucleic acids to displace double-stranded RNA from the arginine patch, increasing turnover and inducing kinetic competition between sRNAs. De novo modeling, biophysical assays and genetic reporter assays show how the C-terminal domain of Hfq increases the stringency and speed of RNA matchmaking.

BIOGRAPHY:

Sarah Woodson is the T.C. Jenkins Professor of Biophysics at Johns Hopkins University. She received her PhD in Biophysical Chemistry in 1987 with Donald Crothers at Yale University, and did postdoctoral research in the laboratory of Thomas Cech at the University of Colorado Boulder from 1987-1990. Her research group studies how RNA molecules fold into specific three-dimensional structures, and how the RNA and proteins components of cellular complexes such as the ribosome come together. In addition to biophysical methods such as X-ray scattering and single-molecule fluorescence, her group has pioneered the application of X-ray hydroxyl radical footprinting to RNA. Dr. Woodson received a Pew Scholar Award in the Biomedical Sciences in 1993, a Camille Dreyfus Teacher-Scholar Award in 1995, was elected an AAAS Fellow in 2010 and the President of the RNA Society (2016-2017).