A unifying model for mTORC1-mediated regulation of mRNA translation
Open accessAbstract
The mTOR complex 1 (mTORC1) kinase nucleates a pathway that promotes cell growth and proliferation and is the target of rapamycin, a drug with many clinical uses. mTORC1 regulates messenger RNA translation, but the overall translational program is poorly defined and no unifying model exists to explain how mTORC1 differentially controls the translation of specific mRNAs. Here we use high-resolution transcriptome-scale ribosome profiling to monitor translation in mouse cells acutely treated with the mTOR inhibitor Torin 1, which, unlike rapamycin, fully inhibits mTORC1 (ref. 2). Our data reveal a surprisingly simple model of the mRNA features and mechanisms that confer mTORC1-dependent translation control. The subset of mRNAs that are specifically regulated by mTORC1 consists almost entirely of transcripts with established 5' terminal oligopyrimidine (TOP) motifs, or, like Hsp90ab1 and Ybx1, with previously unrecognized TOP or related TOP-like motifs that we identified. We find no evidence to support proposals that mTORC1 preferentially regulates mRNAs with increased 5' untranslated region length or complexity. mTORC1 phosphorylates a myriad of translational regulators, but how it controls TOP mRNA translation is unknown. Remarkably, loss of just the 4E-BP family of translational repressors, arguably the best characterized mTORC1 substrates, is sufficient to render TOP and TOP-like mRNA translation resistant to Torin 1. 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. Our results clarify the translational program controlled by mTORC1 and identify 4E-BPs and eIF4G1 as its master effectors.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
qPCR can quantify RP mRNAs transcribed by Pol II but cannot confirm whether they are actively translated by existing ribosomes.
“qPCR can quantify the abundance of these RP mRNAs transcribed by Pol II, but it cannot confirm whether these transcripts are actively being translated by existing ribosomes in the sarcoplasm [75].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [75]
The paper’s Abstract distinguishes transcript abundance from translation: it normalizes ribosome-footprint measurements to mRNA abundance to separate translational and transcriptional regulation. The Methods Summary measures abundance by mRNA profiling, not qPCR; the copy does not specifically discuss Pol II transcription or translation in the sarcoplasm. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe mRNAs encoding the ~80 ribosomal proteins possess a unique 5′ terminal oligopyrimidine tract that strictly regulates their translation via the mTORC1/eIF4E signaling axis.
“The mRNAs encoding the ~80 ribosomal proteins possess a unique 5′ terminal oligopyrimidine (5′ TOP) tract, which strictly regulates their translation via the mTORC1/eIF4E signaling axis [74,75].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [75]
The paper reports that Torin1 suppresses translation of nearly all cytoplasmic ribosomal-protein mRNAs and explains how mTORC1 regulates TOP-mRNA translation through 4E-BPs, eIF4E and eIF4G1 (sections labeled Abstract; page unavailable). It does not establish the stated count of approximately 80 or that the TOP tract is unique to ribosomal-protein mRNAs; it identifies other TOP and TOP-like mRNAs and notes a ribosomal-protein exception, Rps27a. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn923 · Cited by 14,108 · see citing works
Mapping and quantifying mammalian transcriptomes by RNA-Seq
Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L., & Wold, B. (2008) · Nature Methods · doi:10.1038/nmeth.1226 · Cited by 13,696 · see citing works
Epithelial-Mesenchymal Transitions in Development and Disease
Thiery, J. P., Acloque, H., Huang, R. Y. J., & Nieto, M. A. (2009) · Cell · doi:10.1016/j.cell.2009.11.007 · Cited by 9,931 · see citing works
Upstream and downstream of mTOR
Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181 · see citing works
mTOR: from growth signal integration to cancer, diabetes and ageing
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941 · see citing works
Self-citationMammalian microRNAs predominantly act to decrease target mRNA levels
Guo, H., Ingolia, N. T., Weissman, J. S., & Bartel, D. P. (2010) · Nature · doi:10.1038/nature09267 · Cited by 3,886 · see citing works
Genome-Wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling
Ingolia, N. T., Ghaemmaghami, S., Newman, J. R. S., & Weissman, J. S. (2009) · Science · doi:10.1126/science.1168978 · Cited by 3,853 · see citing works
Thoreen, C. C., Kang, S. A., Chang, J. W., Liu, Q., Zhang, J., Gao, Y., Reichling, L. J., Sim, T., Sabatini, D. M., & Gray, N. S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900301200 · Cited by 1,803 · see citing works
Self-citationA Lentiviral RNAi Library for Human and Mouse Genes Applied to an Arrayed Viral High-Content Screen
Moffat, J., Grueneberg, D. A., Yang, X., Kim, S. Y., Kloepfer, A. M., Hinkle, G., Piqani, B., Eisenhaure, T., Luo, B., Grenier, J. K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.01.040 · Cited by 1,803 · see citing works
Self-citationAligning Short Sequencing Reads with Bowtie
Langmead, B. (2010) · Current Protocols in Bioinformatics · doi:10.1002/0471250953.bi1107s32 · Cited by 1,270 · see citing works
Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2
Feldman, M. E., Apsel, B., Uotila, A., Loewith, R., Knight, Z. A., Ruggero, D., & Shokat, K. M. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000038 · Cited by 1,080 · see citing works
DINAMelt web server for nucleic acid melting prediction
Markham, N. R., & Zuker, M. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki591 · Cited by 947 · see citing works
Rapamycin suppresses 5′TOP mRNA translation through inhibition of p70s6k
Jefferies, H. B. J., Fumagalli, S., Dennis, P. B., Reinhard, C., Pearson, R. B., & Thomas, G. (1997) · The EMBO Journal · doi:10.1093/emboj/16.12.3693 · Cited by 934 · see citing works
Choo, A. Y., Yoon, S.-O., Kim, S. G., Roux, P. P., & Blenis, J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809136105 · Cited by 813 · see citing works
Pende, M., Um, S. H., Mieulet, V., Sticker, M., Goss, V. L., Mestan, J., Mueller, M., Fumagalli, S., Kozma, S. C., & Thomas, G. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.8.3112-3124.2004 · Cited by 743 · see citing works
eIF-4E expression and its role in malignancies and metastases
Benedetti, A. D., & Graff, J. R. (2004) · Oncogene · doi:10.1038/sj.onc.1207545 · Cited by 728 · see citing works
mTORC1-Mediated Cell Proliferation, But Not Cell Growth, Controlled by the 4E-BPs
Dowling, R. J. O., Topisirović, I., Alain, T., Bidinosti, M., Fonseca, B. D., Petroulakis, E., Wang, X., Larsson, O. S., Selvaraj, A., Liu, Y., et al. (2010) · Science · doi:10.1126/science.1187532 · Cited by 726 · see citing works
Rapamycin selectively represses translation of the "polypyrimidine tract" mRNA family.
Jefferies, H. B. J., Reinhard, C., Kozma, S. C., & Thomas, G. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.10.4441 · Cited by 623 · see citing works
Lamouille, S., & Derynck, R. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200611146 · Cited by 573 · see citing works
Synthesis of the translational apparatus is regulated at the translational level.
Meyuhas, O. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01719.x · Cited by 570 · see citing works
Gera, J., Mellinghoff, I., Shi, Y.-J., Rettig, M., Tran, C., Hsu, J.-H., Sawyers, C., & Lichtenstein, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309999200 · Cited by 345 · see citing works
Levine, E. M., Becker, Y., Boone, C. W., et al. (1965) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.53.2.350 · Cited by 298 · see citing works
Liu, Q., Chang, J. W., Wang, J., Kang, S. A., Thoreen, C. C., Markhard, A., Hur, W., Zhang, J., Sim, T., Sabatini, D. M., et al. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm101144f · Cited by 257 · see citing works
Self-citationIdentification of the long ubiquitin extension as ribosomal protein S27a
Redman, K. L., & RECHSTEINER, M. C. (1989) · Nature · doi:10.1038/338438a0 · Cited by 245 · see citing works
IRESite—a tool for the examination of viral and cellular internal ribosome entry sites
Mokrejš, M., Mašek, T., Vopálenský, V., Hlubuček, P., Delbos, P., & Pospíšek, M. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp981 · Cited by 207 · see citing works
eIF4GI links nutrient sensing by mTOR to cell proliferation and inhibition of autophagy
Ramírez‐Valle, F., Braunstein, S. E., Zavadil, J., Formenti, S. C., & Schneider, R. J. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200710215 · Cited by 191 · see citing works
Grolleau‐Julius, A., Bowman, J., Pradet‐Balade, B., Puravs, E., Hanash, S., García‐Sanz, J. A., & Beretta, L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202014200 · Cited by 187 · see citing works
A second look at cellular mRNA sequences said to function as internal ribosome entry sites
Kozak, M. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki958 · Cited by 167 · see citing works
Shi, Y., Sharma, A., Wu, H., Lichtenstein, A. K., & Gera, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m407874200 · Cited by 153 · see citing works
Ptushkina, M., von der Haar, T., Vasilescu, S., Frank, R., Birkenhäger, R., & McCarthy, J. E. G. (1998) · The EMBO Journal · doi:10.1093/emboj/17.16.4798 · Cited by 144 · see citing works
Ali, S. M., & Sabatini, D. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500125200 · Cited by 138 · see citing works
Self-citationPatursky-Polischuk, I., Stolovich-Rain, M., Hausner-Hanochi, M., Kasir, J., Cybulski, N., Avruch, J., Rüegg, M. A., Hall, M. N., & Meyuhas, O. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00980-08 · Cited by 135 · see citing works
mTOR‐dependent stimulation of the association of eIF4G and eIF3 by insulin
Harris, T. E., Chi, A., Shabanowitz, J., Hunt, D. F., Rhoads, R. E., & Lawrence, J. C. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601047 · Cited by 133 · see citing works
Iadevaia, V., Caldarola, S., Tino, E., Amaldi, F., & Loreni, F. (2008) · RNA · doi:10.1261/rna.1037108 · Cited by 112 · see citing works
Cap-Assisted Internal Initiation of Translation of Histone H4
Martin, F., Barends, S., Jaeger, S., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2010.12.019 · Cited by 105 · see citing works
Lee, S., & McCormick, F. P. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601268 · Cited by 82 · see citing works
Baert, Y., Goossens, E., Saen, D. V., et al. (2012) · Fertility and Sterility · doi:10.1016/j.fertnstert.2012.02.010 · Cited by 81 · see citing works
Bilanges, B., Argonza-Barrett, R., Kolesnichenko, M., Skinner, C., Nair, M., Chen, M., & Stokoe, D. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.02136-06 · Cited by 69 · see citing works
DBTSS provides a tissue specific dynamic view of Transcription Start Sites
Yamashita, R., Wakaguri, H., Sugano, S., et al. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp1017 · Cited by 60 · see citing works
Atala, A. (2012) · The Journal of Urology · doi:10.1016/j.juro.2012.08.068 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
mTOR Signaling in Growth, Metabolism, and Disease
Saxton, R. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.02.004 · Cited by 7,555 · see citing works
Self-citationMechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028 · see citing works
mTOR at the nexus of nutrition, growth, ageing and disease
Liu, G. Y., & Sabatini, D. M. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0199-y · Cited by 2,737 · see citing works
Self-citationmTOR is a key modulator of ageing and age-related disease
Johnson, S. C., Rabinovitch, P. S., & Kaeberlein, M. (2013) · Nature · doi:10.1038/nature11861 · Cited by 1,676 · see citing works
Nutrient-sensing mechanisms and pathways
Efeyan, A., Comb, W. C., & Sabatini, D. M. (2015) · Nature · doi:10.1038/nature14190 · Cited by 1,110 · see citing works
Self-citationMaking new contacts: the mTOR network in metabolism and signalling crosstalk
Shimobayashi, M., & Hall, M. N. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3757 · Cited by 1,053 · see citing works
Morita, M., Gravel, S.-P., Chénard, V., Sikström, K., Zheng, L., Alain, T., Gandin, V., Avizonis, D., Arguello, M., Zakaria, C., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.10.001 · Cited by 842 · see citing works
Targeting the translation machinery in cancer
Bhat, M., Robichaud, N., Hulea, L., Sonenberg, N., Pelletier, J., & Topisirovic, I. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4505 · Cited by 799 · see citing works
mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype
Herranz, N., Gallage, S., Mellone, M., Wuestefeld, T., Klotz, S., Hanley, C. J., Raguz, S., Acosta, J. C., Innes, A. J., Banito, A., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3225 · Cited by 788 · see citing works
RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer
Wolfe, A. L., Singh, K., Zhong, Y., Drewe, P., Rajasekhar, V. K., Sanghvi, V. R., Mavrakis, K. J., Jiang, M., Roderick, J. E., Van der Meulen, J., et al. (2014) · Nature · doi:10.1038/nature13485 · Cited by 635 · see citing works
mTOR coordinates protein synthesis, mitochondrial activity and proliferation
Morita, M., Gravel, S.-P., Hulea, L., Larsson, O., Pollak, M., St-Pierre, J., & Topisirovic, I. (2015) · Cell Cycle · doi:10.4161/15384101.2014.991572 · Cited by 552 · see citing works
Rapalogs and mTOR inhibitors as anti-aging therapeutics
Lamming, D. W., Ye, L., Sabatini, D. M., & Baur, J. A. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64099 · Cited by 531 · see citing works
Self-citationThe mechanistic target of rapamycin: the grand conducTOR of metabolism and aging
Kennedy, B. K., & Lamming, D. W. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.009 · Cited by 544 · see citing works
Slobodin, B., Han, R., Calderone, V., Vrielink, J. A. F. O., Loayza-Puch, F., Elkon, R., & Agami, R. (2017) · Cell · doi:10.1016/j.cell.2017.03.031 · Cited by 434 · see citing works
Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis
Khajuria, R. K., Munschauer, M., Ulirsch, J. C., Fiorini, C., Ludwig, L. S., McFarland, S. K., Abdulhay, N. J., Specht, H., Keshishian, H., Mani, D. R., et al. (2018) · Cell · doi:10.1016/j.cell.2018.02.036 · Cited by 416 · see citing works
Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics
Leppek, K., Byeon, G. W., Kladwang, W., Wayment-Steele, H. K., Kerr, C. H., Xu, A. F., Kim, D. S., Topkar, V. V., Choe, C., Rothschild, D., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28776-w · Cited by 399 · see citing works
Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics
Leppek, K., Byeon, G. W., Kladwang, W., Wayment-Steele, H. K., Kerr, C. H., Xu, A. F., Kim, D. S., Topkar, V. V., Choe, C., Rothschild, D., et al. (2021) · doi:10.1101/2021.03.29.437587 · Cited by 399 · see citing works
mTOR complexes in neurodevelopmental and neuropsychiatric disorders
Costa-Mattioli, M., & Monteggia, L. M. (2013) · Nature Neuroscience · doi:10.1038/nn.3546 · Cited by 367 · see citing works
Riedl, A., Schlederer, M., Pudelko, K., Stadler, M., Walter, S., Unterleuthner, D., Unger, C., Kramer, N., Hengstschläger, M., Kenner, L., et al. (2016) · Journal of Cell Science · doi:10.1242/jcs.188102 · Cited by 389 · see citing works
New frontiers in translational control of the cancer genome
Truitt, M. L., & Ruggero, D. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.27 · Cited by 378 · see citing works
Targeting the biology of aging with mTOR inhibitors
Mannick, J. B., & Lamming, D. W. (2023) · Nature Aging · doi:10.1038/s43587-023-00416-y · Cited by 372 · see citing works
Targeting the eIF4F Translation Initiation Complex: A Critical Nexus for Cancer Development
Pelletier, J., Graff, J., Ruggero, D., & Sonenberg, N. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2789 · Cited by 367 · see citing works
Translational control in synaptic plasticity and cognitive dysfunction
Buffington, S. A., Huang, W., & Costa-Mattioli, M. (2014) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071013-014100 · Cited by 348 · see citing works
mTOR signaling and its roles in normal and abnormal brain development
Takei, N., & Nawa, H. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00028 · Cited by 317 · see citing works
mTOR signaling in cellular and organismal energetics
Albert, V., & Hall, M. N. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2014.12.001 · Cited by 304 · see citing works
Amino acid-dependent control of mTORC1 signaling: a variety of regulatory modes
Takahara, T., Amemiya, Y., Sugiyama, R., Maki, M., & Shibata, H. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-020-00679-2 · Cited by 300 · see citing works
Interferon-γ regulates cellular metabolism and mRNA translation to potentiate macrophage activation
Su, X., Yu, Y., Zhong, Y., Giannopoulou, E. G., Hu, X., Liu, H., Cross, J. R., Rätsch, G., Rice, C. M., & Ivashkiv, L. B. (2015) · Nature Immunology · doi:10.1038/ni.3205 · Cited by 298 · see citing works
Nucleolar expansion and elevated protein translation in premature aging
Buchwalter, A., & Hetzer, M. W. (2017) · Nature Communications · doi:10.1038/s41467-017-00322-z · Cited by 263 · see citing works
mTORC1 signaling controls multiple steps in ribosome biogenesis
Iadevaia, V., Liu, R., & Proud, C. G. (2014) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2014.08.004 · Cited by 248 · see citing works
GC content shapes mRNA storage and decay in human cells
Courel, M., Clément, Y., Bossevain, C., Foretek, D., Vidal Cruchez, O., Yi, Z., Bénard, M., Benassy, M.-N., Kress, M., Vindry, C., et al. (2019) · eLife · doi:10.7554/elife.49708 · Cited by 250 · see citing works
The cytotoxic T cell proteome and its shaping by the kinase mTOR
Hukelmann, J. L., Anderson, K. E., Sinclair, L. V., Grzes, K. M., Murillo, A. B., Hawkins, P. T., Stephens, L. R., Lamond, A. I., & Cantrell, D. A. (2016) · Nature Immunology · doi:10.1038/ni.3314 · Cited by 249 · see citing works
The mTORC1/4E-BP1 axis represents a critical signaling node during fibrogenesis
Woodcock, H. V., Eley, J. D., Guillotin, D., Platé, M., Nanthakumar, C. B., Martufi, M., Peace, S., Joberty, G., Poeckel, D., Good, R. B., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-07858-8 · Cited by 224 · see citing works
Rubio, C. A., Weisburd, B., Holderfield, M., Arias, C., Fang, E., DeRisi, J. L., & Fanidi, A. (2014) · Genome Biology · doi:10.1186/s13059-014-0476-1 · Cited by 200 · see citing works
Rosario, F. J., Kanai, Y., Powell, T. L., & Jansson, T. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2012.238014 · Cited by 185 · see citing works
HSP90AB1: Helping the good and the bad
Haase, M., & Fitze, G. (2016) · Gene · doi:10.1016/j.gene.2015.08.063 · Cited by 179 · see citing works
Protein synthesis and quality control in aging
Anisimova, A. S., Alexandrov, A. I., Makarova, N. E., Gladyshev, V. N., & Dmitriev, S. E. (2018) · Aging · doi:10.18632/aging.101721 · Cited by 172 · see citing works
Figlia, G., Gerber, D., & Suter, U. (2018) · Glia · doi:10.1002/glia.23273 · Cited by 165 · see citing works
You, J.-S., Mcnally, R. M., Jacobs, B. L., Privett, R. E., Gundermann, D. M., Lin, K.-H., Steinert, N. D., Goodman, C. A., & Hornberger, T. A. (2019) · The FASEB Journal · doi:10.1096/fj.201801653rr · Cited by 149 · see citing works
Regulation of ribosome biogenesis in skeletal muscle hypertrophy
Figueiredo, V. C., & McCarthy, J. J. (2019) · Physiology · doi:10.1152/physiol.00034.2018 · Cited by 140 · see citing works
Translational Control in the Brain in Health and Disease
Sossin, W. S., & Costa-Mattioli, M. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a032912 · Cited by 138 · see citing works
Ribosome biogenesis adaptation in resistance training-induced human skeletal muscle hypertrophy
Figueiredo, V. C., Caldow, M. K., Massie, V., Markworth, J. F., Cameron-Smith, D., & Blazevich, A. J. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00050.2015 · Cited by 133 · see citing works
Role of mTORC1 in mechanically induced increases in translation and skeletal muscle mass
Goodman, C. A. (2019) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01011.2018 · Cited by 133 · see citing works
<scp>TOR</scp>‐mediated regulation of metabolism in aging
Antikainen, H., Driscoll, M., Haspel, G., & Dobrowolski, R. (2017) · Aging Cell · doi:10.1111/acel.12689 · Cited by 122 · see citing works
“, 2013a), ribosomal biogenesis (Thoreen et al., 2012), lipogenesis (Porstmann et al.”
BackgroundExercise-induced skeletal muscle signaling pathways and human athletic performance
Camera, D. M., Smiles, W. J., & Hawley, J. A. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.02.007 · Cited by 128 · see citing works
mTOR complex 1: a key player in neuroadaptations induced by drugs of abuse
Neasta, J., Barak, S., Hamida, S. B., & Ron, D. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12725 · Cited by 114 · see citing works
Wei, Y.-N., Hu, H.-Y., Xie, G.-C., Fu, N., Ning, Z.-B., Zeng, R., & Khaitovich, P. (2015) · Genome Biology · doi:10.1186/s13059-015-0608-2 · Cited by 117 · see citing works
A conserved mechanism of TOR-dependent RCK-mediated mRNA degradation regulates autophagy
Hu, G., McQuiston, T., Bernard, A., Park, Y.-D., Qiu, J., Vural, A., Zhang, N., Waterman, S. R., Blewett, N. H., Myers, T. G., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3189 · Cited by 116 · see citing works
eIF4A supports an oncogenic translation program in pancreatic ductal adenocarcinoma
Chan, K., Robert, F., Oertlin, C., Kapeller-Libermann, D., Avizonis, D., Gutierrez, J., Handly-Santana, A., Doubrovin, M., Park, J., Schoepfer, C., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13086-5 · Cited by 106 · see citing works
p53 induces transcriptional and translational programs to suppress cell proliferation and growth
Loayza-Puch, F., Drost, J., Rooijers, K., Lopes, R., Elkon, R., & Agami, R. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r32 · Cited by 114 · see citing works
Reversal of phenotypes of cellular senescence by pan-mTOR inhibition
Walters, H. E., Deneka-Hannemann, S., & Cox, L. S. (2016) · Aging · doi:10.18632/aging.100872 · Cited by 113 · see citing works
The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders
Mosconi, M. W., Wang, Z., Schmitt, L. M., Tsai, P., & Sweeney, J. A. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00296 · Cited by 112 · see citing works
Genomic sites hypersensitive to ultraviolet radiation
Premi, S., Han, L., Mehta, S., Knight, J., Zhao, D., Palmatier, M. A., Kornacker, K., & Brash, D. E. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1907860116 · Cited by 95 · see citing works
Ribosome biogenesis is necessary for skeletal muscle hypertrophy
Wen, Y., Alimov, A. P., & McCarthy, J. J. (2016) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000082 · Cited by 82 · see citing works
Gaccioli, F., White, V., Capobianco, E., Powell, T. L., Jawerbaum, A., & Jansson, T. (2013) · Biology of Reproduction · doi:10.1095/biolreprod.113.109702 · Cited by 76 · see citing works
Reijnders, M. R. F., Kousi, M., van Woerden, G. M., Klein, M., Bralten, J., Mancini, G. M. S., van Essen, T., Proietti-Onori, M., Smeets, E. E. J., van Gastel, M., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00933-6 · Cited by 76 · see citing works
The role of the TOR pathway in mediating the link between nutrition and longevity
Lushchak, O., Strilbytska, O., Piskovatska, V., Storey, K. B., Koliada, A., & Vaiserman, A. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.03.005 · Cited by 73 · see citing works
The Role of Translation Control in Tumorigenesis and Its Therapeutic Implications
Xu, Y., & Ruggero, D. (2020) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030419-033420 · Cited by 67 · see citing works
Lamming, D. W., Cummings, N. E., Rastelli, A. L., Gao, F., Cava, E., Bertozzi, B., Spelta, F., Pili, R., & Fontana, L. (2015) · Oncotarget · doi:10.18632/oncotarget.5180 · Cited by 69 · see citing works
Anderson, G. R., Wardell, S. E., Cakir, M., Crawford, L., Leeds, J. C., Nussbaum, D. P., Shankar, P. S., Soderquist, R. S., Stein, E. M., Tingley, J. P., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aae0348 · Cited by 53 · see citing works
Evangelisti, C., Cenni, V., & Lattanzi, G. (2016) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12928 · Cited by 53 · see citing works
Identification of a quality-control factor that monitors failures during proteasome assembly
Zavodszky, E., Peak-Chew, S.-Y., Juszkiewicz, S., Narvaez, A. J., & Hegde, R. S. (2021) · Science · doi:10.1126/science.abc6500 · Cited by 45 · see citing works
Heightening Energetic Stress Selectively Targets LKB1-Deficient Non–Small Cell Lung Cancers
Momcilovic, M., McMickle, R., Abt, E., Seki, A., Simko, S. A., Magyar, C., Stout, D. B., Fishbein, M. C., Walser, T. C., Dubinett, S. M., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-0797 · Cited by 46 · see citing works
Coupling between Nutrient Availability and Thyroid Hormone Activation
Lartey, L. J., Werneck-de-Castro, J. P., O-Sullivan, I., Unterman, T. G., & Bianco, A. C. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.665505 · Cited by 41 · see citing works
Zhang, Q., Duplany, A., Moncollin, V., Mouradian, S., Goillot, E., Mazelin, L., Gauthier, K., Streichenberger, N., Angleraux, C., Chen, J., et al. (2019) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12336 · Cited by 31 · see citing works
Bi, C., Zhang, X., Lu, T., Zhang, X., Wang, X., Meng, B., Zhang, H., Wang, P., Vose, J. M., Chan, W. C., et al. (2017) · Haematologica · doi:10.3324/haematol.2016.159160 · Cited by 32 · see citing works
Matrix stiffness regulates lipid nanoparticle-mRNA delivery in cell-laden hydrogels
Athirasala, A., Patel, S., Menezes, P. P., Kim, J., Tahayeri, A., Sahay, G., & Bertassoni, L. E. (2022) · Nanomedicine: Nanotechnology, Biology and Medicine · doi:10.1016/j.nano.2022.102550 · Cited by 16 · see citing works
Muñoz López, M., López-Gil, J. F., Ramírez de la piscina Viúdez, X., Baz-Valle, E., & Tornero Aguilera, J. F. (2026) · Cells · doi:10.3390/cells15111041 · Cited by 1 · see citing works
“…′ TOP) tract, which strictly regulates their translation via the mTORC1/eIF4E signaling axis [74,75]. qPCR can quantify the abundance of these RP mRNAs transcribed by Pol II, but it cannot confirm whether these transcripts are actively being translated by existing ribosomes in the sarcoplasm [75].”
- Authors
- Thoreen, C. C., Chantranupong, L., Keys, H. R., Wang, T., Gray, N. S., & Sabatini, D. M.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Broad Institute (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Corresponding author
- Gray, Nathanael S.
- Sabatini, David M.
- Venue
- Nature
- Published
- 2012-05
- Volume
- 485
- Issue
- 7396
- Pages
- 109-113
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3347774
- OpenAlex
- W2136272779
- Cited by
- 1,477
- References
- 41
- Citations by year
- 2026: 75 · 2025: 87 · 2024: 78 · 2023: 98 · 2022: 97 · 2021: 95 · 2020: 124 · 2019: 123 · 2018: 125 · 2017: 98 · 2016: 103 · 2015: 118 · 2014: 139 · 2013: 93 · 2012: 22
- FWCI
- 47.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- PMC
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (CA129105, CA103866, R01CA103866, R01CA129105)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mTORC1, mRNA translation regulation, 4E-BP1, translational repressor, ribosome profiling, Torin1, rapamycin, prostate cancer, tumor invasion, HSP90AB1, YB-1, mTOR signaling, translational regulation
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Animals, Base Sequence, Gene Expression Regulation, Humans, Male, Models, Biological, Naphthyridines, Phosphorylation, Prostatic Neoplasms, Protein Binding, Proteins, Ribosomes, RNA, Messenger, Protein Biosynthesis, 5' Untranslated Regions, Eukaryotic Initiation Factor-4E, Eukaryotic Initiation Factor-4G, Cell Line, Tumor, Multiprotein Complexes, Mice, TOR Serine-Threonine Kinases, Nucleotide Motifs
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
