Mis‐translation as a potential, new mechanism of adaption and stress response

Abstract

A central tenet of biology is the accurate flow of information from nucleic acids to proteins through the genetic code. It is commonly believed that translation deviating from the genetic code is to be avoided at all times in cells. We have discovered that in contrary, mammalian cells can deliberately reprogram the genetic code with the amino acid methionine upon innate immune activation and chemically triggered oxidative stress. Reprogramming the genetic code with methionine occurs through aminoacylation of non‐methionyl‐tRNAs with methionine in unstressed cells, and is further inducible upon regulated production of the reactive oxygen species (ROS) in the cell. We also found that tRNA misacylation with methionine occurs in all three kingdoms of life, and is highly regulated under cell growth conditions. We propose that mis‐translation via regulated tRNA misacylation is a common mechanism for environmental adaption and for stress response in cells. We are exploring and testing hypotheses on the regulatory mechanism, the biological effects and function of mis‐translation with methionine. The results and conceptual understanding obtained here shall help establish mis‐translation as a new mechanism of stress response in biology.Supported by NIH Director's Pioneer Award (DP1GM105386).