Yi Zhang (Case Western)
Date: Wed. September 17th, 2025, 4:30 pm-5:45 pmLocation: Rockefeller 301
Website: https://sites.google.com/view/zhanglab-cwru/home?authuser=0
From Protein Arginylation to RNA Editing — tRNA and Modifiers Beyond
Translation
Transfer RNAs (tRNAs) are best known for their essential role in ribosome-mediated protein synthesis. Less well known is their role as cofactors in a unique post-translational modification called arginylation, which regulates protein stability, signaling, and quality control. This reaction is catalyzed by ATE1, a conserved enzyme in most eukaryotes, which transfers arginine from arginyl-tRNA onto specific protein substrates. The resulting modification creates degradation signals that route proteins to the proteasome or to autophagy, thereby linking arginyl-tRNAs to broader protein clearance pathways. Our recent work has revealed how ATE1 recognizes its tRNA cofactors and substrates. We are now extending these studies to dissect the tumor suppressor functions of ATE1 and its role in a VHL-independent oxygen-sensing pathway. In parallel, we are developing live-cell biosensors to visualize the dynamics and crosstalk of arginylation with other pathways, and we are exploring a new direction in RNA editing mediated by tRNA-modifying enzymes. Together, our work highlights a unifying theme: tRNAs and their modifiers extend beyond translation to regulate sensing, signaling, and cellular response.
The Zhang lab investigates topics at the interface of chemistry and biology, focusing on elucidating the molecular basis of cellular pathways important for human health and disease biology. Specifically, our research centers on protein and RNA modifications, dissecting their roles in regulating protein homeostasis and chromatin biology, particularly within the contexts of tumor progression and cardiac and neurodegenerative disorders. Through this integrative approach, we aim to understand how post-transcriptional and post-translational modifications impact fundamental cellular processes and disease pathology.