Ariberto FASSATI

Wednesday, 6 November 2019 | 12:00 noon

Professor of Cellular and Molecular Virology, UCL Division of Infection and Immunity, The Rayne Building London, UK

tRNA retrograde transport in response to oxidative stress

(Host: A. Marcello)

In eukaryotes, tRNAs are transcribed in the nucleus and exported to the cytosol, where they deliver amino acids to ribosomes for protein translation. This nuclear-cytoplasmic movement was believed to be unidirectional. However, we discovered that, in human cells, tRNAs can be re-imported into the nucleus by an active mechanism. Others have discovered the same phenomenon in yeast, which has been named “tRNA retrograde transport”. This pathway is conserved in eukaryotes, suggesting a fundamental function; however, little was known about its role in human cells. We recently discovered that oxidative stress triggers tRNA retrograde transport, which is rapid, reversible, and selective for certain tRNA species, mostly with shorter 3’ ends. Retrograde transport of tRNASeC, which promotes translation of selenoproteins required to maintain homeostatic redox levels in cells, is highly efficient. tRNA retrograde transport is regulated by the integrated stress response pathway via the PERK-REDD1-mTOR axis. Thus, tRNA retrograde transport may be part of the cellular response to oxidative stress and may contribute to translational adaptation in conditions of stress.