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000300828 1001_ $$0P:(DE-He78)ef011d4044908051e4d6f0c96e150106$$aHermann, Julia$$b0$$eFirst author$$udkfz
000300828 245__ $$amTORC1 cooperates with tRNA wobble modification to sustain the protein synthesis machinery.
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000300828 520__ $$aSynthesizing the cellular proteome is a demanding process that is regulated by numerous signaling pathways and RNA modifications. How precisely these mechanisms control the protein synthesis machinery to generate specific proteome subsets remains unclear. Here, through genome-wide CRISPR screens we identify genes that enable mammalian cells to adapt to inactivation of the kinase mechanistic target of rapamycin complex 1 (mTORC1), the central driver of protein synthesis. When mTORC1 is inactive, enzymes that modify tRNAs at wobble uridines (U34-enzymes), Elongator and Ctu1/2, become critically essential for cell growth in vitro and in tumors. By integrating quantitative nascent proteomics, steady-state proteomics and ribosome profiling, we demonstrate that the loss of U34-enzymes particularly impairs the synthesis of ribosomal proteins. However, when mTORC1 is active, this biosynthetic defect only mildly affects steady-state protein abundance. By contrast, simultaneous suppression of mTORC1 and U34-enzymes depletes cells of ribosomal proteins, globally inhibiting translation. Thus, mTORC1 cooperates with tRNA U34-enzymes to sustain the protein synthesis machinery and support the high translational requirements of cell growth.
000300828 536__ $$0G:(DE-HGF)POF4-311$$a311 - Zellbiologie und Tumorbiologie (POF4-311)$$cPOF4-311$$fPOF IV$$x0
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000300828 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aMechanistic Target of Rapamycin Complex 1
000300828 650_7 $$09014-25-9$$2NLM Chemicals$$aRNA, Transfer
000300828 650_7 $$2NLM Chemicals$$aRibosomal Proteins
000300828 650_7 $$0WHI7HQ7H85$$2NLM Chemicals$$aUridine
000300828 650_2 $$2MeSH$$aMechanistic Target of Rapamycin Complex 1: metabolism
000300828 650_2 $$2MeSH$$aMechanistic Target of Rapamycin Complex 1: genetics
000300828 650_2 $$2MeSH$$aRNA, Transfer: metabolism
000300828 650_2 $$2MeSH$$aRNA, Transfer: genetics
000300828 650_2 $$2MeSH$$aProtein Biosynthesis
000300828 650_2 $$2MeSH$$aHumans
000300828 650_2 $$2MeSH$$aRibosomes: metabolism
000300828 650_2 $$2MeSH$$aRibosomal Proteins: metabolism
000300828 650_2 $$2MeSH$$aRibosomal Proteins: genetics
000300828 650_2 $$2MeSH$$aHEK293 Cells
000300828 650_2 $$2MeSH$$aAnimals
000300828 650_2 $$2MeSH$$aProteomics
000300828 650_2 $$2MeSH$$aUridine: metabolism
000300828 7001_ $$0P:(DE-He78)da6fb7085973e134322e03d63b6d2028$$aBortecen, Toman$$b1
000300828 7001_ $$00000-0001-7553-4806$$aKalis, Robert$$b2
000300828 7001_ $$0P:(DE-He78)de7b14bf7f622d35c8dabed808304bc9$$aKowar, Alexander$$b3$$udkfz
000300828 7001_ $$00000-0002-4650-4250$$aPechincha, Catarina$$b4
000300828 7001_ $$aVogt, Vivien$$b5
000300828 7001_ $$0P:(DE-He78)0d37cc734b95fed555f2244d6fee6320$$aSchneider, Martin$$b6$$udkfz
000300828 7001_ $$0P:(DE-He78)daaed5a5b968028e6e95d273150d5ab1$$aHelm, Dominic$$b7$$udkfz
000300828 7001_ $$0P:(DE-He78)939d5891259c638c1ab053b1456a578c$$aKrijgsveld, Jeroen$$b8$$udkfz
000300828 7001_ $$0P:(DE-He78)4af0380446b05b5f1995502016151a1b$$aLoayza-Puch, Fabricio$$b9$$udkfz
000300828 7001_ $$00000-0001-8810-6835$$aZuber, Johannes$$b10
000300828 7001_ $$0P:(DE-He78)c8525dbb77cddc5280375ea4a5e3c13e$$aPalm, Wilhelm$$b11$$eLast author$$udkfz
000300828 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-59185-4$$gVol. 16, no. 1, p. 4201$$n1$$p4201$$tNature Communications$$v16$$x2041-1723$$y2025
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