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Recruiting knotty partners: The roles of translation initiation factors in mRNA recruitment to the eukaryotic ribosome

  • Chapter
Ribosomes

Abstract

Eukaryotic translation initiation begins with the binding of a ternary complex (TC) composed of eukaryotic initiation factor (eIF) 2, methionyl initiator tRNA (Met-tRNAi) and GTP to the 40S ribosomal subunit to form the 43S pre-initiation complex (PIC) in a process that is promoted by eIFs 1, 1A, and 3 (Figure 1; for reviews of the entire pathway of translation initiation see (Jackson et al., 2010; Lorsch and Dever, 2010)). This complex is then capable of binding the mRNA near the 5′ end and moving in a 5′-to-3′ direction in search of the start codon. As the start codon in eukaryotic mRNA is usually the first AUG codon, it is necessary for the ribosome to be recruited to the very 5′ end of the mRNA. Were it to bind 3′ to the start codon, it would scan to the next AUG and make an aberrant polypeptide. This localization is achieved by the presence of a 7-methylguanosine cap on the 5′ end of the mRNA that, through a number of protein-protein interactions, brings the ribosome to the very beginning of the mRNA. Protein factors are also thought to be responsible for removing secondary structure and RNA binding proteins from the RNA to create a single-stranded region for the ribosome to bind. Interaction between factors at the 5′ and 3′ ends of the message functionally circularizes the mRNA and allows communication between the ends. After initial recruitment of the PIC, many of these factors are also thought to be involved in the process of scanning, removing structure and proteins so that the ribosome can move forward in search of the start codon, and potentially also pushing the PIC along the mRNA or increasing the directionality of this movement.

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  1. Sarah F. Mitchell
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  2. Sarah E. Walker
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  3. Vaishnavi Rajagopal
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  4. Colin Echeverría Aitken
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  5. Jon R. Lorsch
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Editors and Affiliations

  1. Department of Physical Biochemistry, Max Planck Institute for Biophysical Chemistry, 37077, Göttingen, Germany

    Marina V. Rodnina  & Wolfgang Wintermeyer  & 

  2. Howard Hughes Medical Institute Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Rachel Green

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Mitchell, S.F., Walker, S.E., Rajagopal, V., Aitken, C.E., Lorsch, J.R. (2011). Recruiting knotty partners: The roles of translation initiation factors in mRNA recruitment to the eukaryotic ribosome. In: Rodnina, M.V., Wintermeyer, W., Green, R. (eds) Ribosomes. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0215-2_13

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