Pseudouridine synthase 7 is an opportunistic enzyme that binds and modifies substrates with diverse sequences and structures
Year: 2022
Type: article
Abstract: Significance Pseudouridine is among the most-abundant RNA modifications. We present a framework for conceptualizing how eukaryotic pseudouridine synthases select their substrates. This work reveals the structure of yeast pseudouridine synthase 7 (Pus7) and presents cell-based and biochemical investigations of enzyme binding and activity. We demonstrate that Pus7 interacts promiscuously with RNAs containing UG U AR sequences. Our observations raise the question of why these enzymes only modify <5% of UG U AR sequences in the transcriptome, suggesting that factors beyond inherent enzyme properties—such as protein localization, local RNA structure, and RNA–protein interactions—principally shape Pus7 substrate selection. These findings support a role for Pus7 in providing cells with a mechanism to rapidly alter protein synthesis in response to cellular conditions.
Authors: Meredith K. Purchal, Daniel E. Eyler, Mehmet Tardu, Monika K. Franco, Megan M. Korn, Taslima Khan, Ryan McNassor, Rachel Giles, Katherine Lev, Hari Sharma, Jeremy Monroe, Leena Mallik, Markos Koutmos, Kristin S. Koutmou
Institution: University of Michigan
Language: English
Topic: RNA modifications and cancer
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Awards: G102163711, G107546177, G1313983767, G1664757510, G1947107004, G2287611682, G262962599, G3075337988, G3329398301, G416541740, G4773269573, G498139845, G5607048534, G5906309288, Michigan Chemistry Biology Interface Training Program, G6848031779, G6918803902, G7147508703, Mechanisms of translational control, Michigan Chemistry-Biology Interface Training Program, Structural and functional basis for protein-based eukaryotic RNA processing, G969889393, G993149817
OpenAlex ID: W4206737901