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
Cells face the daunting task of having to maintain the right number of proteins under rapidly changing conditions. One way that they accomplish this is to enzymatically modify all three major classes of biomolecules (DNA, RNA and protein). Chemical modifications to RNAs modulate their structure and function in all organisms, and play central roles in protein synthesis, cell cycle regulation and cell differentiation. Given the conservation and key nature of modifications, it is unsurprising that perturbations to the cellular RNA modification landscape are associated with a wide range of deleterious human health outcomes including cancers, neurological diseases, mitochondrial diseases, and diabetes. While modifications are clearly important, it remains to be discovered how each individual site of modification influences the function of a given RNA. The goal of my research program is to establish the molecular level consequences of RNA chemical modifications on biological processes.
We take a integrated approach, combining the power of mechanistic enzymology, biophysical chemistry, LC-MS/MS, cell-based studies, and genome-wide (ribosome profiling) techniques to investigate the molecular level mechanisms of events that occur when RNAs 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 lab publications
Smith TJ, Tardu M, Koutmou KS. “Sequence and modification status of RNAs in the translation machinery direct ribosome movements during the synthesis of poly(lysine) encoding peptides.” Journal Biological Chemistry (2022), DOI: 10.1016/j.jbc.2022.102039
Purchal MK, Eyler DE, Tardu M, Franco MK, Korn MM, Khan T, McNassor R, Sharma H, Mallik L, Koutmos M, Koutmou KS. “Pseudouridine synthase 7 is an opportunistic enzyme that binds and modifies substrates with diverse sequences and structures.” Proceedings of the National Academy of Sciences (2022), DOI: 10.1073/pnas.2109708119
Jones JD, Monroe J, Koutmou KS. “A molecular level perspective on the frequency, distribution and possible cellular roles of mRNA modifications.” WIREs RNA (2020), DOI: 10.1002/wrna.1586
Eyler DE, Franco MK, Batool Z, Wu MZ, Dubuke ML, Dobosz-Bartoszek M, Jones JD, Polikanov YS, Roy B, Koutmou KS. “Pseudouridinylation of mRNA coding sequences alters translation.” Proceedings of the National Academy of Sciences (2020), DOI: 10.1073/pnas.1821754116
M Tardu, Jones JD, Kennedy RT, Q Lin, KS Koutmou. “Identification and quantification of modified nucleosides in Saccharomyces cerevisiae mRNAs.” ACS Chemical Biology (2019), DOI: 10.1021/acschembio.9b00369
