Seyhan N. Ege Assistant Professor of Chemistry
About
Education/Degrees:
PostDoc Howard Hughes Institute of Medicine at Johns Hopkins School of Medicine (Dept of Molecular Biology and Genetics) Ph.D. University of Michigan (Dept of Chemistry), B.S. University of Colorado at Denver (Dept of Chemistry)
Post-transcriptional control of mRNA expression
The ribosome is the molecular machine responsible for translating mRNA into protein. mRNAs are post-transcriptionally modified and presumably their stability and translatability are affected by these modifications, akin to the post-translational modification (e.g. acetylation, phosphorylation) of proteins. There is emerging evidence suggesting that RNA modifications contribute to a wide variety of diseases including cancer, obesity, heart disease, depression and diabetes. Work in our lab seeks to unlock the ‘RNA epigenetic code’ by uncovering how post-transcriptional modifications alter mRNA structure, translation, and stability, and identifying how the ribonucleoprotein content of different mRNAs is controlled by their modification status.
We take a integrated approach, combining the power of mechanistic enzymology, biophysical chemistry, cell-based studies, and genome-wide (ribosome profiling) techniques to investigate the molecular level mechanisms of events that occur when mRNAs are modified. The breadth of techniques used in our lab uniquely positions us to understand how alterations in translation and translation regulation impact disease.
Representative publications
KS Koutmou, JL Brunelle, S Djuranovic, R Green. “Ribosomes slide on lysine-encoding homopolymeric A stretches.” eLife (2015), PMID 25695637
Arthur L, Pavlovic-Djuranovic S, Koutmou KS, Green R, Szczesny P, Djuranovic S. “Translational control by lysine-encoding A-rich sequences.” Science Advances (2015), PMID 26322332
KS Koutmou, ME McDonald, JL Brunelle, R Green. “RF3:GTP promotes rapid dissociation of the class 1 termination factor.” RNA (2014), PMID 24667215
KS Koutmou, JJ Day-Storms, CA Fierke, “The RNR motif of subtilis RNase P protein interacts with both PRNA and pre-tRNA to stabilize an active conformer,” RNA (2011), PMID 21622899
KS Koutmou, A Casiano-Negroni, M Getz, S Paczini, AJ Andrews, JE Penner-Hahn, HM Al-Hashimi, CA Fierke. “NMR and XAS reveal an inner-sphere metal binding site in the P4 helix of the metallo-ribozyme ribonuclease P,” Proceedings of the National Academy of Sciences (2010), PMID 20133747
KS Koutmou, NH Zahler, JC Kurz, FE Campbell, ME Harris, CA Fierke. “Protein–precursor tRNA contact leads to sequence-specific recognition of 5′ leaders by bacterial ribonuclease P,” Journal of Molecular Biology (2010), PMID 19932118
J Hsieh, KS Koutmou, D Rueda, M Koutmos, NG Walter, CA Fierke, “A divalent cation stabilizes the active conformation of the B. subtilis RNase P•pre-tRNA complex: a role for an inner-sphere metal ion in RNase P,” Journal of Molecular Biology (2010), PMID 20434461
