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The initiation of mammalian protein synthesis and mRNA scanning mechanism.

<div class='caption-title'>The crystal structure of rabbit preinitiation complexes</div>
<div class='caption-title'>Interactions of tRNAi and eIF1A with the 40S subunit</div>
<div class='caption-title'>Path of the mRNA in the 48S PIC</div>
Lomakin IB, Steitz TA
OpenAccess logo Nature 500 307-11 (2013)
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Cited: 128 times
EuropePMC logo PMID: 23873042

Abstract

During translation initiation in eukaryotes, the small ribosomal subunit binds messenger RNA at the 5' end and scans in the 5' to 3' direction to locate the initiation codon, form the 80S initiation complex and start protein synthesis. This simple, yet intricate, process is guided by multiple initiation factors. Here we determine the structures of three complexes of the small ribosomal subunit that represent distinct steps in mammalian translation initiation. These structures reveal the locations of eIF1, eIF1A, mRNA and initiator transfer RNA bound to the small ribosomal subunit and provide insights into the details of translation initiation specific to eukaryotes. Conformational changes associated with the captured functional states reveal the dynamics of the interactions in the P site of the ribosome. These results have functional implications for the mechanism of mRNA scanning.

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  10. Eukaryotic ribosomal protein S3: A constituent of translational machinery and an extraribosomal player in various cellular processes. Graifer D, Malygin A, Zharkov DO, Karpova G. Biochimie 99 8-18 (2014)
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  16. Roles of ribosomal proteins in the functioning of translational machinery of eukaryotes. Graifer D, Karpova G. Biochimie 109 1-17 (2015)
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  19. Control of Translation at the Initiation Phase During Glucose Starvation in Yeast. Janapala Y, Preiss T, Shirokikh NE. Int J Mol Sci 20 E4043 (2019)
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  21. Extensions, Extra Factors, and Extreme Complexity: Ribosomal Structures Provide Insights into Eukaryotic Translation. Weisser M, Ban N. Cold Spring Harb Perspect Biol 11 a032367 (2019)
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  25. Structural Insights into tRNA Dynamics on the Ribosome. Agirrezabala X, Valle M. Int J Mol Sci 16 9866-9895 (2015)
  26. Interaction of tRNA with eukaryotic ribosome. Graifer D, Karpova G. Int J Mol Sci 16 7173-7194 (2015)
  27. RNA-Binding Proteins as Regulators of Internal Initiation of Viral mRNA Translation. López-Ulloa B, Fuentes Y, Pizarro-Ortega MS, López-Lastra M. Viruses 14 188 (2022)
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  29. Eukaryote-specific extensions in ribosomal proteins of the small subunit: Structure and function. Ghosh A, Komar AA. Translation (Austin) 3 e999576 (2015)
  30. Two "Edges" in Our Knowledge on the Functions of Ribosomal Proteins: The Revealed Contributions of Their Regions to Translation Mechanisms and the Issues of Their Extracellular Transport by Exosomes. Ochkasova A, Arbuzov G, Malygin A, Graifer D. Int J Mol Sci 24 11458 (2023)

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