Oxidative stress triggers selective tRNA retrograde transport in human cells

In eukaryotes, tRNAs are transcribed in the nucleus and exported to the cytosol where they deliver aminoacids to ribosomes for protein translation. This nuclear-cytoplasmic movement was believed to be unidirectional. However, recent discoveries demonstrated an active shuttling of tRNAs between cytosol and nucleus, named tRNA retrograde transport. This pathway is conserved in eukaryotes, suggesting a fundamental function, however little is known about its role in human cells. Here we report that, in human cells, oxidative stress triggers tRNA retrograde transport, which is rapid and reversible. Next generation sequencing of tRNAs revealed that retrograde transport is selective for certain tRNA species, mostly with shorter 3’ ends. mTOR and PERK regulate tRNA nuclear import, linking it to the endoplasmic reticulum unfolded protein response. Thus tRNA retrograde transport is a new component of the cellular response to oxidative stress.