Post-translational N-terminal Arginylation of Protein Fragments: A Pivotal Portal to Proteolysis

The majority of tRNA studies has focused on tRNA molecules as pivotal player in the fundamental process of protein synthesis. Mounting studies have unveiled further functions for tRNA beyond protein synthesis, including non-ribosomal amino acid transfer, and regulation of targeted proteolysis. Post-translational N-terminal arginylation of protein fragments, a non-ribosomal amino acid transfer, is one of the crucial ways by which tRNA participates in various protein degradation trajectories and influences global cellular functions. Previous studies demonstrated a role of arginylation by arginyltransferases (ATEs) in protein degradation, autophagy, and cell death in mammalian cells. Notably, recent investigations in plants have revealed some of the crucial aspects regarding the biochemical nature of N-terminal arginylation and some of its physiological roles. Herein, we review some of the key data on N-terminal arginylation of protein fragments with respect to targeted proteolysis in mammalian cells. Future mechanistic studies using state of the art approaches and physiologically-relevant cellular models are warranted to enhance our molecular understanding of this important yet enigmatic protein modification.