The mTORC1 complex supports cell growth and proliferation in response to energy 
levels, growth factors, and nutrients. The Rag guanosine triphosphatases 
(GTPases) activate mTORC1 in response to amino acids by promoting its 
redistribution to lysosomes. In this paper, we identify a novel role for Rags in 
controlling activation of transcription factor EB (TFEB), a master regulator of 
autophagic and lysosomal gene expression. Interaction of TFEB with active Rag 
heterodimers promoted recruitment of TFEB to lysosomes, leading to 
mTORC1-dependent phosphorylation and inhibition of TFEB. The interaction of TFEB 
with Rags required the first 30 residues of TFEB and the switch regions of the 
Rags G domain. Depletion or inactivation of Rags prevented recruitment of TFEB 
to lysosomes, whereas expression of active Rags induced association of TFEB with 
lysosomal membranes. Finally, Rag GTPases bound and regulated activation of 
microphthalmia-associated transcription factor, suggesting a broader role for 
Rags in the control of gene expression. Our work provides new insight into the 
molecular mechanisms that link nutrient availability and TFEB localization and 
activation.