Harnett, D. et al. A critical period of translational control during brain development at codon resolution. Nat. Struct. Mol. Biol. 29, 1277–1290 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schwanhäusser, B. et al. Global quantification of mammalian gene expression control. Nature 473, 337–342 (2011).

Article  PubMed  Google Scholar 

Byrne, R., Levin, J. G., Bladen, H. A. & Nirenberg, M. W. The in vitro formation of a DNA–ribosome complex. Proc. Natl Acad. Sci. USA 52, 140–148 (1964).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kohler, R., Mooney, R. A., Mills, D. J., Landick, R. & Cramer, P. Architecture of a transcribing–translating expressome. Science 356, 194–197 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, C. et al. Structural basis of transcription–translation coupling. Science 369, 1359–1365 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Webster, M. W. et al. Structural basis of transcription–translation coupling and collision in bacteria. Science 369, 1355–1359 (2020).

Article  CAS  PubMed  Google Scholar 

Aitken, C. E. & Lorsch, J. R. A mechanistic overview of translation initiation in eukaryotes. Nat. Struct. Mol. Biol. 19, 568–576 (2012).

Article  CAS  PubMed  Google Scholar 

Hashem, Y. & Frank, J. The jigsaw puzzle of mRNA translation initiation in eukaryotes: a decade of structures unraveling the mechanics of the process. Annu. Rev. Biophys. https://doi.org/10.1146/annurev-biophys-070816-034034 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Hinnebusch, A. G. The scanning mechanism of eukaryotic translation initiation. Annu. Rev. Biochem. 83, 779–812 (2014).

Article  CAS  PubMed  Google Scholar 

Valášek, L. S. et al. Embraced by eIF3: structural and functional insights into the roles of eIF3 across the translation cycle. Nucleic Acids Res. 45, 10948–10968 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Bohlen, J., Fenzl, K., Kramer, G., Bukau, B. & Teleman, A. A. Selective 40S footprinting reveals cap-tethered ribosome scanning in human cells. Mol. Cell https://doi.org/10.1016/j.molcel.2020.06.005 (2020). This study presents the first clear evidence that scanning can be cap-tethered in human cells.

Article  PubMed  Google Scholar 

Brito Querido, J. et al. Structure of a human 48S translational initiation complex. Science 369, 1220–1227 (2020). This structure reveals how eIF4F interacts with the 43S complex.

Article  CAS  PubMed  Google Scholar 

Chiluiza, D., Bargo, S., Callahan, R. & Rhoads, R. E. Expression of truncated eukaryotic initiation factor 3e (eIF3e) resulting from integration of mouse mammary tumor virus (MMTV) causes a shift from cap-dependent to cap-independent translation. J. Biol. Chem. 286, 31288–31296 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Grifo, J. A., Tahara, S. M., Morgan, M. A., Shatkin, A. J. & Merrick, W. C. New initiation factor activity required for globin mRNA translation. J. Biol. Chem. 258, 5804–5810 (1983).

Article  CAS  PubMed  Google Scholar 

Kumar, P., Hellen, C. U. T. & Pestova, T. V. Toward the mechanism of eIF4F-mediated ribosomal attachment to mammalian capped mRNAs. Genes Dev. 30, 1573–1588 (2016). This study presents strong evidence to support the threading model of mRNA recruitment to the 43S complex in mammals.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Llácer, J. L. et al. Conformational differences between open and closed states of the eukaryotic translation initiation complex. Mol. Cell 59, 399–412 (2015).

Article  PubMed  PubMed Central  Google Scholar 

Marintchev, A. et al. Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation. Cell 136, 447–460 (2009).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pestova, T. V. & Kolupaeva, V. G. The roles of individual eukaryotic translation initiation factors in ribosomal scanning and initiation codon selection. Genes Dev. 16, 2906–2922 (2002).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brito Querido, J. et al. The structure of a human translation initiation complex reveals two independent roles for the helicase eIF4A. Nat. Struct. Mol. Biol. https://doi.org/10.1038/s41594-023-01196-0 (2024). This study reveals that in addition to the eIF4A molecule that is part of the eIF4F complex, there is a second molecule of eIF4A in the 48S complex, which functions separately from eIF4F.

Villa, N., Do, A., Hershey, J. W. B. & Fraser, C. S. Human eukaryotic initiation factor 4G (eIF4G) protein binds to eIF3c, -d, and -e to promote mRNA recruitment to the ribosome. J. Biol. Chem. 288, 32932–32940 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Berthelot, K., Muldoon, M., Rajkowitsch, L., Hughes, J. & McCarthy, J. E. G. Dynamics and processivity of 40S ribosome scanning on mRNA in yeast. Mol. Microbiol. 51, 987–1001 (2004).

Article  CAS  PubMed  Google Scholar 

Kozak, M. Role of ATP in binding and migration of 40S ribosomal subunits. Cell 22, 459–467 (1980).

Article  CAS  PubMed  Google Scholar 

Nielsen, K. H. et al. Functions of eIF3 downstream of 48S assembly impact AUG recognition and GCN4 translational control. EMBO J. 23, 1166–1177 (2004).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shirokikh, N. E., Dutikova, Y. S., Staroverova, M. A., Hannan, R. D. & Preiss, T. Migration of small ribosomal subunits on the 5’ untranslated regions of capped messenger RNA. Int. J. Mol. Sci. 20, 4464 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Simonetti, A., Guca, E., Bochler, A., Kuhn, L. & Hashem, Y. Structural insights into the mammalian late-stage initiation complexes. Cell Rep. 31, 107497 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, J. et al. Rapid 40S scanning and its regulation by mRNA structure during eukaryotic translation initiation. Cell 185, 4474–4487 (2022). This study reveals the kinetics of scanning and finds that multiple copies of eIF4A can have a role during mRNA recruitment.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yi, S.-H. et al. Conformational rearrangements upon start codon recognition in human 48S translation initiation complex. Nucleic Acids Res. 50, 5282–5298 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

García-García, C., Frieda, K. L., Feoktistova, K., Fraser, C. S. & Block, S. M. Factor-dependent processivity in human eIF4A DEAD-box helicase. Science 348, 1486–1488 (2015).

Article  PubMed  PubMed Central  Google Scholar 

Sen, N. D., Zhou, F., Harris, M. S., Ingolia, N. T. & Hinnebusch, A. G. eIF4B stimulates translation of long mRNAs with structured 5′ UTRs and low closed-loop potential but weak dependence on eIF4G. Proc. Natl Acad. Sci. USA 113, 10464–10472 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shahbazian, D. et al. Control of cell survival and proliferation by mammalian eukaryotic initiation factor 4B. Mol. Cell Biol. 30, 1478–1485 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Calviello, L. et al. DDX3 depletion represses translation of mRNAs with complex 5′ UTRs. Nucleic Acids Res. 49, 5336–5350 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gupta, N., Lorsch, J. R. & Hinnebusch, A. G. Yeast Ded1 promotes 48S translation pre-initiation complex assembly in an mRNA-specific and eIF4F-dependent manner. eLife 7, e38892 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Pisareva, V. P., Pisarev, A. V., Komar, A. A., Hellen, C. U. T. & Pestova, T. V. Translation initiation on mammalian mRNAs with structured 5′ UTRs requires DExH-box protein DHX29. Cell 135, 1237–1250 (2008).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang, B. Y. & Fernández, I. S. Long-range interdomain communications in eIF5B regulate GTP hydrolysis and translation initiation. Proc. Natl Acad. Sci. USA 117, 1429–1437 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lapointe, C. P. et al. eIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining. Nature 607, 185–190 (2022). This study reveals how eIF5B coordinates with eIF1A to reorient the tRNA and allow joining of the 60S ribosome subunit.

Article  CAS  PubMed  PubMed Central