The DOI matches its Crossref record; 137 of the 137 references it cites were found in a registry or an index.
Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets
Open accessAbstract
Translational control in eukaryotic cells is critical for gene regulation during nutrient deprivation and stress, development and differentiation, nervous system function, aging, and disease. We describe recent advances in our understanding of the molecular structures and biochemical functions of the translation initiation machinery and summarize key strategies that mediate general or gene-specific translational control, particularly in mammalian systems.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Both transcription and translation are strongly affected by exact DNA and mRNA sequences, respectively, as well as their cellular environments (Sonenberg and Hinnebusch, 2009; Alpert et al., 2017).”
From Evaluating Efficiencies of Dual AAV Approaches for Retinal Targeting (2017) · cites this paper as Sonenberg and Hinnebusch, 2009
Experimental — accuracy not yet measuredIn the citing paper
“Translation of a uORFs can modulate the expression of the downstream protein-coding gene in response to global (Sonenberg and Hinnebusch, 2009) or gene-specific regulatory signals (Medenbach et al., 2011).”
From Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity and Dynamics of Mammalian Proteomes (2011) · cites this paper as Sonenberg and Hinnebusch, 2009
In the citing paper
“which, like NIBAN1, phosphorylates EIF4EBP1 to allow assembly of the initiation complex23”
From NEAT-seq: simultaneous profiling of intra-nuclear proteins, chromatin accessibility and gene expression in single cells (2022) · cites this paper as [23]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
(2008) · doi:10.1038/nrg2290 · Cited by 5,199 · cited 1×
“Even for those studies concluding that inhibition occurs at the level of translation initiation, the data are conflicting as in some studies translation inhibition was cap dependent and mediated by eIF4F, whereas in others it was cap independent and mediated via eIF6 (Filipowicz et al., 2008).”
Self-citationThe impact of microRNAs on protein output
Baek, D., Villén, J., Shin, C., Camargo, F. D., Gygi, S. P., & Bartel, D. P. (2008) · Nature · doi:10.1038/nature07242 · Cited by 3,592
Widespread changes in protein synthesis induced by microRNAs
Selbach, M., Schwanhäusser, B., Thierfelder, N., Fang, Z., Khanin, R., & Rajewsky, N. (2008) · Nature · doi:10.1038/nature07228 · Cited by 3,429 · cited 1×
“It is noteworthy that recent large-scale studies in cells demonstrated that the magnitude of translation inhibition of most mRNAs is moderate (~2-fold) (Baek et al., 2008; Selbach et al., 2008), and that similar results were obtained in cell-free translation extracts.”
Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation
Vasudevan, S., Tong, Y., & STEITZ, J. A. (2007) · Science · doi:10.1126/science.1149460 · Cited by 2,911 · cited 1×
“Surprisingly, it was reported recently that miRNAs can also stimulate rather than inhibit translation when cells enter quiescence (Vasudevan et al., 2007).”
Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells
Vattem, K. M., & Wek, R. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400541101 · Cited by 1,696
Specificity of microRNA target selection in translational repressionPreprint
Doench, J. G., & Sharp, P. A. (2004) · Genes & Development · doi:10.1101/gad.1184404 · Cited by 1,685
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
Um, S. H., Frigerio, F., Watanabe, M., Picard, F., Joaquin, M., Sticker, M., Fumagalli, S., Allegrini, P. R., Kozma, S. C., Auwerx, J., et al. (2004) · Nature · doi:10.1038/nature02866 · Cited by 1,677
A microRNA in a Multiple-Turnover RNAi Enzyme Complex
Hutvágner, G., & Zamore, P. D. (2002) · Science · doi:10.1126/science.1073827 · Cited by 1,674
Argonaute2, a Link Between Genetic and Biochemical Analyses of RNAi
Hammond, S. M., Boettcher, S., Caudy, A. A., Kobayashi, R., & Hannon, G. J. (2001) · Science · doi:10.1126/science.1064023 · Cited by 1,580
Single-Stranded Antisense siRNAs Guide Target RNA Cleavage in RNAi
Martînez, J., Patkaniowska, A., Urlaub, H., Lührmann, R., & Tuschl, T. (2002) · Cell · doi:10.1016/s0092-8674(02)00908-x · Cited by 1,480 · cited 1×
“Once processed from its primary transcript precursor, an miRNA is then loaded into a protein complex, referred to as an RNA-induced silencing complex (RISC), which targets and inhibits protein expression from specific mRNAs (Hammond et al., 2001; Hutvagner and Zamore, 2002; Martinez et al., 2002).”
Cited by
Sorted by citations
Items 301–400 of 1,050
mRNA translation in astrocytes controls hippocampal long-term synaptic plasticity and memory
Sharma, V. K., Oliveira, M. M., Sood, R., Khlaifia, A., Lou, D., Hooshmandi, M., Hung, T.-Y., Mahmood, N., Reeves, M., Ho-Tieng, D., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2308671120 · Cited by 26
“…β , and γ subunits), together with GTP and the initiator tRNA (Met - tRNAi Met ), forms the ternary complex (TC), which binds to the 40S ribosomal subunit to facilitate its engagement with the mRNA initiation codon (3, 5, 13). eIF2 α phosphoryl ation (p - eIF2 α ) engenders a decrease in TC (14).”
BackgroundSelf-citationChen, M., Fang, Y., Liang, M., Zhang, N., Zhang, X., Xu, L., Ren, X., Zhang, Q., Zhou, Y., Peng, S., et al. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04103-9 · Cited by 47
“Because 4E-BP1 is a canonical translational repressor that inhibit eIF4E-mediated translation initiation and the consistency between the levels of phosphorylated 4E-BP1 and DNMT1 [21], we hypothesized that DNMT1 might be a downstream effector of 4E-BP1.”
BackgroundCytoplasmic Isoleucyl tRNA synthetase as an attractive Multi-stage antimalarial drug target
Istvan, E., Guerra, F., Abraham, M., Huang, K.-S., Rocamora, F., Zhao, H., Xu, L., Pasaje, C., Kumpornsin, K., Luth, M., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adc9249 · Cited by 24
Lu, B. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.970654 · Cited by 28
“After initiation codon recognition, the 60S large ribosome is joined and 80S ribosome is formed (Sonenberg and Hinnebusch, 2009).”
MethodRegulatory role of RNA N6-methyladenosine modifications during skeletal muscle development
Yu, B., Liu, J., Zhang, J., Mu, T., Feng, X., Ma, R., & Gu, Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.929183 · Cited by 26
Thorstensen, M., Turko, A., Heath, D., Jeffries, K., & Pitcher, T. (2022) · bioRxiv · doi:10.1101/2022.02.20.481219 · Cited by 24
“While the rate-limiting step for protein synthesis is often the initiation of translation (Sonenberg and Hinnebusch, 2009; Spriggs et al., 2010), transcription regulation is another key element of the stress response (De Nadal et al., 2011).”
Systemic ablation of vitamin D receptor leads to skeletal muscle glycogen storage disorder in mice
Das, A., Gopinath, S. D., & Arimbasseri, G. A. (2021) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12841 · Cited by 29
The elongation factor eEF1A2 controls translation and actin dynamics in dendritic spines
Mendoza, M. B., Gutierrez, S., Ortiz, R., Moreno, D. F., Dermit, M., Dodel, M., Rebollo, E., Bosch, M., Mardakheh, F. K., & Gallego, C. (2021) · Science Signaling · doi:10.1126/scisignal.abf5594 · Cited by 29
Dawson, J. E., Bah, A., Zhang, Z., Vernon, R. M., Lin, H., Chong, P. A., Vanama, M. S., Sonenberg, N., Gradinaru, C. C., & Forman-Kay, J. D. (2020) · Nature Communications · doi:10.1038/s41467-020-16783-8 · Cited by 33
Self-citationDecoding Parkinson’s Disease Pathogenesis: The Role of Deregulated mRNA Translation
Martin, I. (2016) · Journal of Parkinson’s Disease · doi:10.3233/jpd-150738 · Cited by 23
Wolin, E., Guo, J. K., Blanco, M. R., Goronzy, I. N., Gorhe, D., Dong, W., Perez, A. A., Keskin, A., Valenzuela, E., Abdou, A. A., et al. (2025) · Cell · doi:10.1016/j.cell.2025.06.042 · Cited by 35
“The TOP-motif score intervals are [0, 1), [1, 2), [2, 3), [3, inf).”
N6-methyladenosine RNA methylation in diabetic kidney disease
Huang, J., Yang, F., Liu, Y., & Wang, Y. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116185 · Cited by 24
Liu, Q., Fong, B., Yoo, S., Unruh, J. R., Guo, F., Yu, Z., Chen, J., Si, K., Li, R., & Zhou, C. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2300475120 · Cited by 28
“One of these membrane-less condensates is the stress-induced protein aggregate, which is a common product of protein misfolding stemming from the loss of proteostasis under environmental stresses and pathological conditions (3–9).”
BackgroundmRNA Translation Is Dynamically Regulated to Instruct Stem Cell Fate
Wang, R., & Amoyel, M. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.863885 · Cited by 23
Wang, C., Leavenworth, J. D., Zhang, C., Liu, Z., Yuan, K. Y., Wang, Y., Zhang, G., Wang, S., Cui, X., Zhang, Y., et al. (2022) · Oncogene · doi:10.1038/s41388-022-02272-3 · Cited by 28
“eIF4A1 unwinds secondary and tertiary structures of G-quadruplexes in the 5′ UTR to facilitate translation of the coded proteins [4].”
Endocrine Fibroblast Growth Factors in Relation to Stress Signaling
Shimizu, M., & Sato, R. (2022) · Cells · doi:10.3390/cells11030505 · Cited by 25
“Unlike during ER stress and oxidative stress, general control non-derepressible 2 (GCN2) phosphorylates eIF2α, leading to an increase in ATF4 translation [189].”
BackgroundDouble stranded DNA breaks and genome editing trigger loss of ribosomal protein RPS27A
Riepe, C., Zelin, E., Frankino, P. A., Meacham, Z. A., Fernandez, S. G., Ingolia, N. T., & Corn, J. E. (2021) · FEBS Journal · doi:10.1111/febs.16321 · Cited by 27
Cavallo, F., Troglio, F., Fagà, G., Fancelli, D., Shyti, R., Trattaro, S., Zanella, M., D’Agostino, G., Hughes, J. M., Cera, M. R., et al. (2020) · Molecular Autism · doi:10.1186/s13229-020-00387-6 · Cited by 23
Ionizing Radiation and Translation Control: A Link to Radiation Hormesis?
Kabilan, U., Graber, T. E., Alain, T., & Klokov, D. Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186650 · Cited by 35
The TOR Pathway at the Neuromuscular Junction: More Than a Metabolic Player?
Castets, P., Ham, D. J., & Rüegg, M. A. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00162 · Cited by 29
Phenotypic effects of paralogous ribosomal proteins bL31A and bL31B in E. coli
Lilleorg, S., Reier, K., Volõnkin, P., Remme, J., & Liiv, A. (2020) · Scientific Reports · doi:10.1038/s41598-020-68582-2 · Cited by 23
Li, Y., Cao, Y., Wang, J., Fu, S., Cheng, J., Ma, L., Zhang, Q. H., Guo, W., Kan, X., & Liu, J. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.29325 · Cited by 25
“Eukaryotic translation initiation factor 4EBP1 binds to EIF4E, which is bound at the 5′ cap of mRNA, preventing the formation of the translation initiation complex (Sonenberg & Hinnebusch, 2009).”
BackgroundSun, C., Xu, X., Chen, Z., Zhou, F., Wang, W. J., Chen, J.-Z., Sun, M., Wang, F., Jiang, L., Ji, M., et al. (2025) · Nature Cell Biology · doi:10.1038/s41556-024-01607-4 · Cited by 23
“The initiation, elongation and termination of translation are tightly regulated by interactions between ribosomes and their associated factors, such as RNA binding proteins (RBPs) 9,10 .”
Yu, Y., Yang, Y., Chen, X., Chen, Z., Zhu, J., & Zhang, J. (2024) · Advanced Science · doi:10.1002/advs.202309712 · Cited by 16
Jia, X., Wang, P.-L., Huang, C., Zhao, D., Wu, Q., Lu, B., Nie, W.-N., Huang, L., Tian, X., Li, P., et al. (2023) · Journal of experimental & clinical cancer research : CR · doi:10.1186/s13046-023-02666-5 · Cited by 22
“In most cancers, aberrant regulation of the translation machinery results in the abnormal synthesis of molecules that could potentially enhance cell proliferation [7, 8].”
BackgroundDeng, M., Wang, N., Li, Z., Chen, R., Duan, J., Peng, Y., Wu, Z., Zhang, Z., Jiang, L., Zheng, X. F. S., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04614-1 · Cited by 25
Translational control in cell ageing: an update
Woodward, K., & Shirokikh, N. E. (2021) · Biochemical Society Transactions · doi:10.1042/bst20210844 · Cited by 21
A prion accelerates proliferation at the expense of lifespan
Garcia, D. M., Campbell, E., Jakobson, C. M., Tsuchiya, M., (23811802), E. A. S., DiNardo, A. L., Kaeberlein, M. R., & Jarosz, D. F. (2021) · eLife · doi:10.7554/elife.60917 · Cited by 25
“Translation is a rate- limiting step for growth in many organisms (Polymenis and Schmidt, 1997; Sonenberg, 1993) and is often activated in human cancers (Sonenberg and Hinnebusch, 2009).”
Neuroimmune Consequences of eIF4E Phosphorylation on Chemotherapy-Induced Peripheral Neuropathy
Agalave, N. M., Mody, P. H., Szabo-Pardi, T. A., Jeong, H. S., & Burton, M. D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.642420 · Cited by 21
Singh, G., Fritz, S. E., Seufzer, B. J., & Boris‐Lawrie, K. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.012005 · Cited by 27
“The eIF4E-dependent messenger ribonucleoproteins (mRNPs) activate polysome assembly and steady-state protein synthesis (17).”
BackgroundKrušič, A., Mencin, N., Leban, M., Nett, E., Perković, M., Şahin, U., Megušar, P., Štrancar, A., & Sekirnik, R. (2025) · Molecular Therapy: Nucleic Acids · doi:10.1016/j.omtn.2025.102491 · Cited by 21
“7 Previously reported IP-RP mRNA work was performed with non-porous particle chromatographic supports, which may have contributed to the limitations observed in (1) scalability, since extremely low porosity of the material generates high back-pressures for chromatographic experiments, reducing…”
Metabolic rewiring during bone development underlies tRNA m7G–associated primordial dwarfism
Li, Q., Jiang, S., Lei, K., Han, H. L., Chen, Y., Lin, W., Xiong, Q., Qi, X., Gan, X., Sheng, R., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci177220 · Cited by 27
“For analysis of Wdr4 R215L/R215L translation by phosphorylating 4E-BPs (38, 56).”
The Nuclear Cap-Binding Complex, a multitasking binding partner of RNA polymerase II transcripts
Kataoka, N. (2023) · Journal of Biochemistry (Tokyo) · doi:10.1093/jb/mvad081 · Cited by 21
“Mainly, translation in eukaryotes is dependent on the cytoplasmic cap-binding protein eIF4E, which initiates translation by recruiting the 40S small ribosomal subunit (9) .”
BackgroundInfluentialCDK13 phosphorylates the translation machinery and promotes tumorigenic protein synthesis
Wu, C., Xie, T., Guo, Y., Wang, D., Qiu, M., Han, R., Qing, G., Liang, K., & Liu, H. (2023) · Oncogene · doi:10.1038/s41388-023-02653-2 · Cited by 22
“Cap-dependent translation initiation is a rate-limiting step that is controlled by eIF4E-binding proteins (4EBPs) [20].”
BackgroundHigh-Resolution Mapping of Transcription Initiation in the Asexual Stages of Toxoplasma gondii
Markus, B. M., Waldman, B. S., Lorenzi, H., & Lourido, S. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.617998 · Cited by 23
“Since 5′ leaders are associated with mechanisms of post-transcriptional regulation (Wilkie et al., 2003; Sonenberg and Hinnebusch, 2009; Jackson et al., 2010), the elongation of these non-coding regions may have contributed to increased regulatory complexity.”
BackgroundSARS-CoV-2 infected cells present HLA-I peptides from canonical and out-of-frame ORFsPreprint
Weingarten-Gabbay, S., Klaeger, S., Sarkizova, S., Pearlman, L., Chen, D.-Y., Bauer, M., Taylor, H. B., Conway, H. L., Tomkins-Tinch, C., Finkel, Y., et al. (2020) · bioRxiv · doi:10.1101/2020.10.02.324145 · Cited by 21
“For example, viruses can attenuate translation of host proteins, downregulate the proteasome machinery, and interfere with HLA-I expression (Hansen and Bouvier, 2009; Sonenberg and Hinnebusch, 2009).”
BackgroundLegere, R. M., Cohen, N. D., Poveda, C., Bray, J. M., Barhoumi, R., Szule, J. A., de la Concha-Bermejillo, A., Bordin, A. I., & Pollet, J. (2021) · Scientific Reports · doi:10.1038/s41598-020-79855-1 · Cited by 20
The integrated stress response regulates 18S nonfunctional rRNA decay in mammals
Coria, A. R., Shah, A., Shafieinouri, M., Taylor, S. J., Orgebin, E., Guiblet, W. M., Miller, J. T., Sharma, I. M., & Wu, C. C. (2025) · Molecular Cell · doi:10.1016/j.molcel.2025.01.017 · Cited by 36
Regulating translation in aging: from global to gene-specific mechanisms
Solyga, M., Majumdar, A., & Besse, F. (2024) · EMBO Reports · doi:10.1038/s44319-024-00315-2 · Cited by 23
Endoplasmic reticulum stress associates with the development of intervertebral disc degeneration
Huang, J., Zhou, Q., Ren, Q., Luo, L., Ji, G., & Zheng, T. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1094394 · Cited by 23
Li, K., Kong, J., Zhang, S., Zhao, T., & Qian, W. (2022) · Genome biology · doi:10.1186/s13059-022-02829-1 · Cited by 23
“To synthesize functional proteins and maintain protein homeostasis, the genetic information carried by messenger RNAs (mRNAs) must be faithfully transmitted to proteins [1].”
BackgroundAxonal mRNA localization and translation: local events with broad roles
Li, L., Yu, J., & Ji, S. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03995-4 · Cited by 25
Sequence determinants as key regulators in gene expression of T cells
Nicolet, B. P., Zandhuis, N. D., Lattanzio, V. M., & Wolkers, M. C. (2021) · Immunological Reviews · doi:10.1111/imr.13021 · Cited by 23
RNA-Binding Proteins at the Host-Pathogen Interface Targeting Viral Regulatory Elements
Embarc-Buh, A., Francisco-Velilla, R., & Martínez-Salas, E. (2021) · Viruses · doi:10.3390/v13060952 · Cited by 20
“High levels of P-eIF2α hampers GDP/GTP exchange in the ternary complex, and thus, inefficient delivery of the initiator Met-tRNAi [25].”
BackgroundInfluentialDysregulation of translational control signaling in autism spectrum disorders
Hooshmandi, M., Wong, C., & Khoutorsky, A. (2020) · Cellular Signalling · doi:10.1016/j.cellsig.2020.109746 · Cited by 17
Bera, A., & Lewis, S. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21114075 · Cited by 22
The G3BP stress-granule proteins reinforce the integrated stress response translation programme
Smith, J., & Bartel, D. P. (2025) · Nature Cell Biology · doi:10.1038/s41556-025-01834-3 · Cited by 31
“Many of these mRNAs contain upstream open reading frames (uORFs), which can help regulate their translation during stress 38 .”
Xiang, Y., & Dong, X. (2025) · Annual Review of Phytopathology · doi:10.1146/annurev-phyto-121823-032335 · Cited by 29
“Despite its importance, translational regulation remains less studied than transcriptional regulation, largely due to the complexity of the process (23, 76, 171).”
PACT prevents aberrant activation of PKR by endogenous dsRNA without sequestration
Ahmad, S., Zou, T., Hwang, J., Zhao, L., Wang, X., Davydenko, A., Buchumenski, I., Zhuang, P., Fishbein, A. R., Capcha-Rodriguez, D., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-58433-x · Cited by 29
“Furthermore, the varying levels of phosphorylation by PKR did not simply correlate with the number of surface-exposed Ser/Thr residues (43, 28, 34, and 25 for PACT, Δ DRBD1, Δ DRBD2, and Δ DRBD3, respectively), further arguing against non-speci fi c phosphorylation.”
Emerging Mechanisms of Human Mitochondrial Translation Regulation
Brischigliaro, M., Ahn, A., Hong, S.-W., Fontanesi, F., & Barrientos, A. (2025) · TIBS -Trends in Biochemical Sciences. Regular ed · doi:10.1016/j.tibs.2025.03.007 · Cited by 19
The FGF/FGFR/c-Myc axis as a promising therapeutic target in multiple myeloma
Giacomini, A., Taranto, S., Gazzaroli, G., Faletti, J., Capoferri, D., Marcheselli, R., Sciumé, M., Presta, M., Sacco, A., & Roccaro, A. M. (2024) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-024-03217-2 · Cited by 19
“This phosphorylation blocks the ability of 4EBP1 to inhibit the translation initiation factor eIF4E, thus promoting the recruitment of the 40S ribosomal subunit to the 5 ′ -cap of mRNAs and enhancing translation initiation [71].”
BackgroundGeng, J., Li, S., Li, Y., Wu, Z., Bhurtel, S., Rimal, S., Khan, D., Ojha, R., Brandman, O., & Lu, B. (2024) · Nature Communications · doi:10.1038/s41467-024-45525-3 · Cited by 30
Protein kinase double-stranded RNA-dependent (PKR) in antiviral defence in fish and mammals.
Chaumont, L., Collet, B., & Boudinot, P. (2023) · Developmental and Comparative Immunology · doi:10.1016/j.dci.2023.104732 · Cited by 19
Patil, S. S., Chalkiadaki, K., Mergiya, T. F., Krimbacher, K., Amorim, I. S., Akerkar, S., Gkogkas, C., & Bramham, C. (2023) · iScience · doi:10.1016/j.isci.2023.106649 · Cited by 19
“Translation initiation, the multistep process by which the ribosome is recruited to mRNA, is tightly regulated and often rate-limiting for protein synthesis.(14) Eukaryotic translation initiation factor 4E (eIF4E), which binds to the 50-terminal cap structure of cytoplasmic mRNA, plays a key role in both the process a…”
BackgroundZhao, P., Yao, R.-Q., Zheng, L., Wu, Y., Li, Y., Dong, N., Li, J., Du, X., & Yao, Y.-M. (2022) · Burns & Trauma · doi:10.1093/burnst/tkac055 · Cited by 18
“Although ribosomes may have translation folding errors or be exposed to various stresses from inside and outside the cell [39,40], as precision-assembled organelles,”
BackgroundChen, X., Xu, Q., Yue, Y., Duan, Y., Liu, H., Chen, X.-L., Huang, J.-B., & Zheng, L. (2023) · Plant Communications · doi:10.1016/j.xplc.2023.100550 · Cited by 19
“Cytosolic translation can be regulated by viral infection in animal cells (Sonenberg and Hinnebusch, 2009).”
BackgroundAnsari, S. A., Dantoft, W., Ruiz‐Orera, J., Syed, A. P., Blachut, S., van Heesch, S., Hübner, N., & Uhlenhaut, N. H. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.09.042 · Cited by 22
“It is known that RBPs bind post-transcriptionally to target mRNAs and regulate their stability, distribution and translation into corresponding protein products [63,64].”
BackgroundNucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells
Chen, M., Long, Q., Borrie, M. S., Sun, H.-H., Zhang, C.-L., Yang, H., Shi, D., Gartenberg, M. R., & Deng, W. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009899 · Cited by 19
“(eIF2α) on serine 51 hampers the turnover of the eIF2-bound GDP to GTP, thus impeding the formation of the eIF2-GTP-tRNA ternary complex and the initiation of protein synthesis [48].”
BackgroundThe Role of mRNA Translational Control in Tumor Immune Escape and Immunotherapy Resistance
Cerezo, M., Robert, C., Liu, L., & Shen, S. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-1466 · Cited by 26
Blazie, S. M., Takayanagi-Kiya, S., McCulloch, K. A., & Jin, Y. (2021) · eLife · doi:10.7554/elife.68336 · Cited by 24
Alexander, M. R., Brice, A. M., van Vuren, P. J., Rootes, C. L., Tribolet, L., Cowled, C. J., Bean, A. G. D., & Stewart, C. R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073392 · Cited by 32
“virally encoded Nsp1 [45] and host encoded 4E-BP1 [64] should be less effective on closed loop mRNAs.”
BackgroundChhipi-Shrestha, J. K., Schneider-Poetsch, T., Suzuki, T., Mito, M., Khan, K., Dohmae, N., Iwasaki, S., & Yoshida, M. (2020) · bioRxiv · doi:10.1101/2020.11.23.393835 · Cited by 19
Ucha, M., Roura‐Martínez, D., Ambrosio, E., & Higuera‐Matas, A. (2020) · Journal of Psychopharmacology · doi:10.1177/0269881120944159 · Cited by 20
“…the mRNA and the ribosome and regulating transcription (for an excellent review about initiation factors and regulation of protein translation see Sonenberg and Hinnebusch, 2009). mTORC1 mediates the phosphorylation of elongation initiation factor 4E binding proteins (eIF4EBP1, eIF4EBP2 and…”
BackgroundRoles of the Translation Initiation Factor eIF2α Phosphorylation in Cell Structure and Function
Back, S. H. (2020) · Cell Structure and Function · doi:10.1247/csf.20013 · Cited by 19
“Regardless of the type of stimulus, eIF2α phosphorylation causes an identical reduc‐ tion in global protein synthesis (Donnelly et al. , 2013; Sonenberg and Hinnebusch, 2009; Wek et al. , 2006) (Fig.”
BackgroundSynthetic Biology of Plants and Microbes for Agriculture, Environment, and Future Applications
Clauer, P. R., Nou, A., Toth, T., Yu, Q., Chemla, Y., Boo, A., Yoon, K. S., & Voigt, C. A. (2026) · Chemical Reviews · doi:10.1021/acs.chemrev.4c00687 · Cited by 21
Unlocking the Potential of Chemically Modified Nucleic Acid Therapeutics
Gao, J., Nutan, B., Gargouri, D., Pisal, N. D., Do, V., Zubair, M., Alanzi, H., Wang, H., Lee, D., Joshi, N., et al. (2024) · Advanced Therapeutics · doi:10.1002/adtp.202400231 · Cited by 20
Integrated stress response activator halofuginone protects mice from diabetes-like phenotypes
Rai, S., Szaruga, M., Pitera, A. P., & Bertolotti, A. (2024) · The Journal of Cell Biology · doi:10.1083/jcb.202405175 · Cited by 17
“GCN2 is activated by amino acid shortage, PKR by double-stranded RNA during viral infections, and HRI by heme deficiency (Sonenberg and Hinnebusch, 2009; Wek, 2018).”
InfluentialUpstream open reading frames: new players in the landscape of cancer gene regulation
Dasgupta, A., & Prensner, J. R. (2024) · NAR Cancer · doi:10.1093/narcan/zcae023 · Cited by 19
“This scanning mechanism of translation begins at the 5 end of the mRNA, at the 7-methylguanosine (m 7 G) cap structure ( 18 , 20 , 21 ).”
BackgroundLiu, C., Chen, L., Cong, Y., Cheng, L., Shuai, Y., Lv, F., Chen, K., Song, Y., & Xing, Y. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06489-w · Cited by 19
“Phosphorylation of EIF2S1 suppresses global translation, while phosphorylation of eukaryotic translation initiation factor 4E binding protein 1 (4EBP1) releases EIF4E and initiates translation [17].”
Wurtzel, J. G. T., Lazar, S., Askari, S., Zhao, X., Severa, J. R., Ayombil, F., Michael, J. V., Camire, R. M., McKenzie, S. E., Stalker, T. J., et al. (2024) · Blood Advances · doi:10.1182/bloodadvances.2023011734 · Cited by 25
“15,16 17-22 None of these pathways has been investigated in resting platelets exposed to plasma GFHs, and constitutive platelet translation and the regenerating proteome have not been explored.”
Moghaddam, M. M., Fazel, P., Fallah, A., Sedighian, H., Kachuei, R., Behzadi, E., & Fooladi, A. A. I. (2023) · Stem Cell Reviews and Reports · doi:10.1007/s12015-023-10594-2 · Cited by 18
“Released exosomes are taken up by target cells through endocytosis, direct membrane fusion, and receptor-ligand interaction [45] exosomes showed that miRNAs can be directly delivered to target cells through exosomes and thereby cause functional regulation of mRNA targets in the cell [64].”
BackgroundA Th17 cell-intrinsic glutathione/mitochondrial-IL-22 axis protects against intestinal inflammationPreprint
Bonetti, L., Horková, V., Longworth, J., Guerra, L., Kurniawan, H., Franchina, D. G., Soriano-Baguet, L., Grusdat, M., Spath, S., Koncina, E., et al. (2023) · bioRxiv · doi:10.1101/2023.07.06.547932 · Cited by 18
“One mTOR target is the repressor of translation 4E-BP1. mTOR-dependent phosphorylation of 4E-BP1 induces the dissociation from translation initiation factor eIF4E, which then initiates protein translation (Sonenberg and Hinnebusch, 2009).”
BackgroundThe central role of translation elongation in response to stress
Barros, G. C., Guerrero, S., & Silva, G. M. (2023) · Biochemical Society Transactions · doi:10.1042/bst20220584 · Cited by 22
Frias, E. S., Hoseini, M. S., Krukowski, K., Paladini, M. S., Grue, K. A., Ureta, G., Rienecker, K. D. A., Walter, P., Stryker, M. P., & Rosi, S. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2209427119 · Cited by 19
“The phosphorylation-mediated central regulatory step leads to a reduction in global protein translation and to the translational up-regulation of a select subset of mRNAs, such as activating transcription factor 4 (ATF4) (44, 45).”
BackgroundSavu, D., & Moisoi, N. (2022) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2022.148588 · Cited by 20
Witte, F., Ruiz‐Orera, J., Mattioli, C. C., Blachut, S., Adami, E., Schulz, J. F., Schneider-Lunitz, V., Hummel, O., Patone, G., Mücke, M. B., et al. (2021) · Genome biology · doi:10.1186/s13059-021-02397-w · Cited by 16
Çetin, B., & O’Leary, S. E. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac631 · Cited by 20
“eIF4G also directly contacts the 43S PIC (10).”
BackgroundSaxena, A. K., Bhardwaj, N., Chilkoti, G. T., Malik, A., Thakur, G., Bajaj, M., Banerjee, A., Banerjee, B. D., & Singal, A. (2021) · Pain Medicine · doi:10.1093/pm/pnab142 · Cited by 22
Li, Y., Tang, J., Ji, X., Hua, M.-M., Liu, M., Chang, L., Gu, Y.-H., Shi, C., Ni, W.-H., Liu, J., et al. (2021) · Development · doi:10.1242/dev.190793 · Cited by 18
Krassnig, S., Wohlrab, C., Golob-Schwarzl, N., Raicht, A., Schatz, C., Birkl-Toeglhofer, A., Skofler, C., Gantenbein, N., Leoni, M., Asslaber, M., et al. (2021) · Cancers · doi:10.3390/cancers13061482 · Cited by 18
“The initiation process starts with the formation of the 43S preinitiation complex (PIC) under the assistance of the eIF3 complex, eIF1 and eIF1A [9,10].”
BackgroundCeci, M., Fazi, F., & Romano, N. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.166046 · Cited by 21
Dysregulated translational control in brain disorders: from genes to behavior
Wiebe, S. A., Nagpal, A., & Sonenberg, N. (2020) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.05.005 · Cited by 24
“Another mechanism regulating eIF4E activity is through competitive binding of the 4E-BPs for a conserved sequence shared by the 4E-BPs and eIF4G, thereby inhibiting translation initiation [22] (Figure 1).”
BackgroundSelf-citationRecent Advances in Messenger Ribonucleic Acid (mRNA) Vaccines and Their Delivery Systems: A Review
Belay, W. Y., Nibret, G., & Aschale, Y. (2023) · Clinical Pharmacology Advances and Applications · doi:10.2147/cpaa.s418314 · Cited by 16
Jian, H., Wen, S., Liu, R., Zhang, W., Li, Z., Chen, W., Zhou, Y., Khassanov, V. T., Mahmoud, A. M. A., Wang, J., et al. (2023) · Plants · doi:10.3390/plants12122232 · Cited by 17
“Translation regulation does not need to generate new messenger RNA, so it is a fast and direct way to cope with adverse environments [42].”
BackgroundGenome-scale CRISPR–Cas9 screen reveals novel regulators of B7-H3 in tumor cells
Zhao, S., Wang, Y., Yang, N., Mu, M., Wu, Z., Li, H., Tang, X., Zhong, K., Zhang, Z., Huang, C., et al. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-004875 · Cited by 18
“47 48 51 Our findings demonstrate that constitutive activation of the p38-eIF4E signaling axis is responsible for both TNF-α stimulation and SP20H depletion-induced B7-H3 expression, thus providing additional evidence that eIF4E facilitates abnormal gene expression.”
Vasudevan, D., Katow, H., Huang, H.-W., Tang, G., & Ryoo, H. D. (2021) · Disease Models & Mechanisms · doi:10.1242/dmm.049119 · Cited by 18
“Such phosphorylation of eIF2 α leads to decreased availability of Met-tRNA iMet , resulting in lowered cellular translation (Sonenberg and Hinnebusch, 2009).”
Dysregulated mRNA Translation in the G2019S LRRK2 and LRRK2 Knock-Out Mouse Brains
Kim, J. W., Yin, X., Martin, I., Xiong, Y., Eacker, S. M., Ingolia, N. T., Dawson, T. M., & Dawson, V. L. (2021) · eNeuro · doi:10.1523/eneuro.0310-21.2021 · Cited by 17
“Translation initiation is a tightly regulated process, with many eukaryotic initiation factors (eIFs) involved in the regulation and facilitation of the process (Sonenberg and Hinnebusch, 2009; Jackson et al., 2010).”
BackgroundWu, T., Lei, Y., Jin, S., Zhao, Q. S., Cheng, W., Xi, Y., Wang, L., Wang, Z., Niu, X., & Chen, G. (2021) · Molecular Immunology · doi:10.1016/j.molimm.2021.02.008 · Cited by 18
Cao, Y., Zhang, Y., Ma, L., Wang, J., Guo, W., Cheng, J., Hu, G., Fu, S., & Liu, J. (2021) · Cell and Tissue Research · doi:10.1007/s00441-020-03355-x · Cited by 18
Luo, Z., Hu, H., Liu, S., Zhang, Z., Li, Y., & Zhou, L. (2020) · RNA Biology · doi:10.1080/15476286.2020.1827193 · Cited by 21
“Although modulations in all stages of translation work together to affect the production of protein, changes controlling translation initiation seem to be critically important [11,12].”
BackgroundChaturvedi, N. K., Kling, M. J., Griggs, C. N., Kesherwani, V., Shukla, M., McIntyre, E. M., Ray, S., Liu, Y., McGuire, T. R., Sharp, J. G., et al. (2020) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-19-0996 · Cited by 20
TNF-alpha: Roles in pathogenesis and therapeutics in cancer
Valenzuela-Cardenas, M., & Nowicki, T. S. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.111251 · Cited by 18
“…rapid translation upon activation by phosphorylation of eukaryotic initiation factor 4E (eIF4E) by mechanistic target of rapamycin, leading to its binding to TNF-α mRNA 5 ′ structures, which facilitates formation of the preinitiation complex, allowing it to be translated by ribosomes (81, 82).”
Discovery of highly potent dual GSPT1/BRD4 degraders with anti-AML activity.
Xu, Y., Yang, H., Li, Y.-X., Qi, Y.-Y., Zhao, F., Hong, Y.-H., Cheng, B.-B., Lu, Z.-B., Zhang, J., Guo, C., et al. (2025) · European journal of medicinal chemistry · doi:10.1016/j.ejmech.2025.117381 · Cited by 16
eIF4F-mediated dysregulation of mRNA translation in cancer
Amiri, M., Mahmood, N., Tahmasebi, S., & Sonenberg, N. (2025) · RNA · doi:10.1261/rna.080340.124 · Cited by 14
“Because of its pivotal role as a rate-limiting factor, multiple mechanisms evolved to regulate the activity of eIF4E, either through posttranslational modifications by kinases or by direct protein – protein interactions. eIF4E is controlled primarily by two key signaling pathways: (1) the phosphoinositide 3-kinase (PI…”
InfluentialSelf-citationInsights into the Mode and Mechanism of Interactions Between RNA and RNA-Binding Proteins
Fang, Y., Liu, X.-Y., Liu, Y.-L., & Xu, N.-Y. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252111337 · Cited by 16
“Notably, the mRNA translation requires the activation of eukaryotic initiation factors (eIFs) to recognize the mRNA’s m7G cap structure at the 5 ′ end or the poly(A) tail at the 3 ′ end [85], which means that mRNA-binding proteins can regulate eIFs to affect the translation process.”
BackgroundTadic, S., & Martı́nez, A. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1433185 · Cited by 19
“On the other hand, UTRs, 5´-cap and poly-A tail are functional non-coding parts of mRNA molecule crucial for its maturation, translation but also stability and timely-removal, thus modifying these structures can lead to improved functionality of mRNA based therapeutics (142 – 145).”
Coding circular RNA in human cancer
Lin, Y., Wang, Y., Li, L., & Zhang, K. (2024) · Genes & Diseases · doi:10.1016/j.gendis.2024.101347 · Cited by 15
eIF4A1 enhances LARP1-mediated translational repression during mTORC1 inhibition
Shichino, Y., Yamaguchi, T., Kashiwagi, K., Mito, M., Takahashi, M., Ito, T., Ingolia, N. T., Kuba, K., & Iwasaki, S. (2024) · Nature Structural & Molecular Biology · doi:10.1038/s41594-024-01321-7 · Cited by 17
“Eukaryotic cells harness a number of eukaryotic translation initiation factors (eIFs) to achieve accurate and efficient initiation 3 .”
Anderle, N., Schäfer-Ruoff, F., Staebler, A., Kersten, N., Koch, A., Önder, C. E., Keller, A., Liebscher, S., Hartkopf, A., Hahn, M., et al. (2023) · Journal of experimental & clinical cancer research : CR · doi:10.1186/s13046-023-02782-2 · Cited by 16
“…of TNBC-PDMs consistent with those in the literature, characterized by upregulated PI3K/Akt and MAPK/RTK signaling [53, 63, 64, 98] with overexpressed proteins associated with integrated stress response [99–102], higher relapse rates, mortality [64, 103, 104], tumor growth and EMT [29, 105–107].”
BackgroundEnhanced bypass of PD-L1 translation reduces the therapeutic response to mTOR kinase inhibitors
Cao, Y., Ye, Q., Ma, M., & She, Q. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112764 · Cited by 18
Metadata
- Authors
- Sonenberg, N., & Hinnebusch, A. G.
- Affiliations
- McGill University (CA)
- National Institutes of Health (US)
- Corresponding author
- Sonenberg, Nahum
- Hinnebusch, Alan G.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 136
- Issue
- 4
- Pages
- 731-745
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3610329
- OpenAlex
- W2037313242
- Cited by
- 3,304
- References
- 137
- Citations by year
- 2026: 145 · 2025: 144 · 2024: 166 · 2023: 194 · 2022: 187 · 2021: 219 · 2020: 208 · 2019: 204 · 2018: 211 · 2017: 240 · 2016: 199 · 2015: 188 · 2014: 212 · 2013: 212 · 2012: 222
- FWCI
- 14.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship@McGill (McGill) (submittedVersion, cc-by-nc-nd)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (1ziahd001004-27, ZIA HD001004)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- 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 Research and Splicing
- Keywords
- translation initiation, translational regulation, nutrient deprivation, stress response, nervous system function, aging, disease, mammalian cells
- MeSH terms
- Animals, Gene Expression Regulation, Humans, Models, Molecular, Peptide Chain Initiation, Translational, Peptide Initiation Factors, Ribosomes
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
