A unifying model for mTORC1-mediated regulation of mRNA translation The mTOR Complex 1 (mTORC1) kinase promotes cell growth and proliferation and is targeted by the drug rapamycin. mTORC1 regulates mRNA translation, but the overall translational program is poorly defined. This study uses high-resolution transcriptome-scale ribosome profiling to monitor translation in cells treated with the mTOR inhibitor Torin1, which fully inhibits mTORC1. These data reveal a simple view of the mRNA features and mechanisms that confer mTORC1-dependent translation control. The subset of mRNAs specifically regulated by mTORC1 consists almost entirely of transcripts with established 5' terminal oligopyrimidine (TOP) motifs or previously unrecognized TOP or related TOP-like motifs. The study finds no evidence to support the proposal that mTORC1 preferentially regulates mRNAs with increased 5' UTR length or complexity. mTORC1 phosphorylates a myriad of translational regulators, but how it controls TOP mRNA translation is unknown. Remarkably, loss of the well-characterized mTORC1 substrates, the 4E-BP family of translational repressors, is sufficient to render TOP and TOP-like mRNA translation resistant to Torin1. The 4E-BPs inhibit translation initiation by interfering with the interaction between the cap-binding protein eIF4E and eIF4G1. Loss of this interaction diminishes the capacity of eIF4E to bind TOP and TOP-like mRNAs much more than other mRNAs, explaining why mTOR inhibition selectively suppresses their translation. The study clarifies the translational program controlled by mTORC1 and identifies 4E-BPs and eIF4G1 as its master effectors. mTORC1 is the catalytic subunit of two complexes, mTOR Complex 1 and 2 (mTORC1/2), that regulate growth and are often deregulated in disease. mTORC1 is the allosteric target of the well-known drug rapamycin, which has clinical uses in organ transplantation, cardiology, and oncology. A major function of mTORC1 is to regulate protein synthesis, which it is thought to control through several substrates, including the S6 kinases, the inhibitory eIF4E-binding proteins (4E-BPs), and the eIF4G initiation factors. ATP-competitive inhibitors of mTOR such as Torin1 impair protein synthesis and proliferation to much greater degrees than rapamycin, largely due to their inhibition of rapamycin-resistant functions of mTORC1. Because earlier efforts to identify mRNAs translationally regulated by mTORC1 relied on rapamycin, it is likely that the mTORC1-regulated translational program is not fully defined. As a step towards defining this program, the study examined the effects of Torin1A unifying model for mTORC1-mediated regulation of mRNA translation The mTOR Complex 1 (mTORC1) kinase promotes cell growth and proliferation and is targeted by the drug rapamycin. mTORC1 regulates mRNA translation, but the overall translational program is poorly defined. This study uses high-resolution transcriptome-scale ribosome profiling to monitor translation in cells treated with the mTOR inhibitor Torin1, which fully inhibits mTORC1. These data reveal a simple view of the mRNA features and mechanisms that confer mTORC1-dependent translation control. The subset of mRNAs specifically regulated by mTORC1 consists almost entirely of transcripts with established 5' terminal oligopyrimidine (TOP) motifs or previously unrecognized TOP or related TOP-like motifs. The study finds no evidence to support the proposal that mTORC1 preferentially regulates mRNAs with increased 5' UTR length or complexity. mTORC1 phosphorylates a myriad of translational regulators, but how it controls TOP mRNA translation is unknown. Remarkably, loss of the well-characterized mTORC1 substrates, the 4E-BP family of translational repressors, is sufficient to render TOP and TOP-like mRNA translation resistant to Torin1. The 4E-BPs inhibit translation initiation by interfering with the interaction between the cap-binding protein eIF4E and eIF4G1. Loss of this interaction diminishes the capacity of eIF4E to bind TOP and TOP-like mRNAs much more than other mRNAs, explaining why mTOR inhibition selectively suppresses their translation. The study clarifies the translational program controlled by mTORC1 and identifies 4E-BPs and eIF4G1 as its master effectors. mTORC1 is the catalytic subunit of two complexes, mTOR Complex 1 and 2 (mTORC1/2), that regulate growth and are often deregulated in disease. mTORC1 is the allosteric target of the well-known drug rapamycin, which has clinical uses in organ transplantation, cardiology, and oncology. A major function of mTORC1 is to regulate protein synthesis, which it is thought to control through several substrates, including the S6 kinases, the inhibitory eIF4E-binding proteins (4E-BPs), and the eIF4G initiation factors. ATP-competitive inhibitors of mTOR such as Torin1 impair protein synthesis and proliferation to much greater degrees than rapamycin, largely due to their inhibition of rapamycin-resistant functions of mTORC1. Because earlier efforts to identify mRNAs translationally regulated by mTORC1 relied on rapamycin, it is likely that the mTORC1-regulated translational program is not fully defined. As a step towards defining this program, the study examined the effects of Torin1