Wobble tRNA modifications and mTORC1 cooperate to generate the protein synthesis machinery. (RiboSeq)

Synthesizing the cellular proteome is a demanding process that is regulated by numerous signaling pathways and RNA modifications. How these orchestrate the protein synthesis machinery to generate specific proteome subsets remains unclear. We found when mTORC1 was inactive, tRNA wobble uridine-modifying enzymes (U34-enzymes) Elongator and Ctu1/2 became essential for cell growth in vitro and in tumors. Using ribosome profiling, RNA seq and other methods, we interrogated the functional interplay between U34-enzymes and mTORC1.EPP2 murine pancreatic cancer cell lines, with induced KO of Ctu1 or Elp3 in combination with Torin1 or DMSO treatment, was carried out to better understand th role of RNA modifications and mTORC1 in codon-specific translation