A University of Michigan team of biochemists, led by Kristin Koutmou, Ph.D., and Markos Koutmos, Ph.D., Assistant Professors in the Department of Chemistry and Department of Biophysics, is reframing the understanding of the biology of a class of enzymes called Pseudouridine Synthases (Pus enzymes). These enzymes modify many types of RNAs, and the Koutmou and Koutmos Labs’ research brings new insights into the selection principles that guide modification incorporation. Their results are published in the Proceedings of the National Academy of Sciences (PNAS).
This novel understanding of pseudouridine biology could have important therapeutic implications because the dysregulation of Pus enzymes is linked to inherited diseases impacting muscle and brain function, such as progressive mitochondrial myopathy and sideroblastic anemia (MLASA). Furthermore, these enzymes also catalyze pseudouridine incorporation into RNA viral genomes, including that of SARS-CoV-2. As such, Pus enzymes present a potential new target for the development of therapeutics.
Since RNAs are central to the protein synthesis machinery, its chemical modifications can alter how fast and/or how accurately proteins are made. These modifications can have many consequences for cellular health, overall cellular adaptation, and cellular regulation. [Read more…] about Koutmou and Koutmos results published in the Proceedings of the National Academy of Sciences (PNAS)