43S preinitiation complex

The 43S preinitiation complex (43S PIC) is a ribonucleoprotein complex that exists during an early step of eukaryotic translation initiation. The 43S PIC contains the small ribosomal subunit (40S) bound by the initiation factors eIF1, eIF1A, eIF3, and the eIF2-Met-tRNA _i^Met-GTP ternary complex (eIF2-TC). ^{[1] [2] [3] [4]}

Function

The 43S is an important intermediate complex during cap-dependent initiation in translation. In the canonical model of translation initiation, the 43S PIC is pre-formed as a stable complex and recruited to the 5' cap of eukaryotic messenger RNAs (mRNAs) by the eIF4F complex. ^{[2] [3] [5]} The 43S PIC then "scans" in the 5' --> 3' direction along the mRNA in an ATP-dependent fashion (via eIF4A and/or other RNA helicases such as Ded1/DDX3 and DHX29) to locate the start codon. Start codon recognition occurs through base-pairing between the Met-tRNA_i^Met and AUG in the ribosomal P-site and a number of associated changes, and is followed by joining of the large 60S ribosomal subunit to form the 80S ribosome.

Structure

Due to its size and complexity, the 43S PIC has eluded high resolution structural characterization. However, combined approaches including cryo-EM, cross-linking, and the structural characterization of individual components, has led to models for the complex organization. ^{[6] [7] [8]}

See also

• 40S ribosomal subunit
• eIF3

References

1. Sonenberg, Nahum; Hinnebusch, Alan G. (2009). "Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets". Cell. 136 (4). Elsevier BV: 731–745. doi:10.1016/j.cell.2009.01.042. ISSN   0092-8674. PMC   3610329 . PMID   19239892.
2. Aitken, Colin E.; Lorsch, Jon R. (2012). "A mechanistic overview of translation initiation in eukaryotes". Nat. Struct. Mol. Biol. 19 (6): 568–576. doi:10.1038/nsmb.2303. PMID   22664984. S2CID   9201095.
3. Fraser, Christopher S. (2015). "Quantitative studies of mRNA recruitment to the eukaryotic ribosome". Biochimie. 114. Elsevier BV: 58–71. doi:10.1016/j.biochi.2015.02.017. ISSN   0300-9084. PMC   4458453 . PMID   25742741.
4. Hinnebusch, Alan G. (2017). "Structural Insights into the Mechanism of Scanning and Start Codon Recognition in Eukaryotic Translation Initiation". Trends in Biochemical Sciences. 42 (8). Elsevier BV: 589–611. doi:10.1016/j.tibs.2017.03.004. ISSN   0968-0004. PMID   28442192.
5. Sokabe, Masaaki; Fraser, Christopher S. (2014-09-22). "Human Eukaryotic Initiation Factor 2 (eIF2)-GTP-Met-tRNAiTernary Complex and eIF3 Stabilize the 43 S Preinitiation Complex". Journal of Biological Chemistry. 289 (46). American Society for Biochemistry & Molecular Biology (ASBMB): 31827–31836. doi: 10.1074/jbc.m114.602870 . ISSN   0021-9258. PMC   4231660 . PMID   25246524.
6. Hashem, Yaser; des Georges, Amedee; Dhote, Vidya; Langlois, Robert; Liao, Hstau Y.; Grassucci, Robert A.; Hellen, Christopher U.T.; Pestova, Tatyana V.; Frank, Joachim (2013). "Structure of the Mammalian Ribosomal 43S Preinitiation Complex Bound to the Scanning Factor DHX29". Cell. 153 (5). Elsevier BV: 1108–1119. doi:10.1016/j.cell.2013.04.036. ISSN   0092-8674. PMC   3730827 . PMID   23706745.
7. Erzberger, Jan P.; Stengel, Florian; Pellarin, Riccardo; Zhang, Suyang; Schaefer, Tanja; Aylett, Christopher H.S.; Cimermančič, Peter; Boehringer, Daniel; Sali, Andrej; Aebersold, Ruedi; Ban, Nenad (2014). "Molecular Architecture of the 40S⋅eIF1⋅eIF3 Translation Initiation Complex". Cell. 158 (5). Elsevier BV: 1123–1135. doi:10.1016/j.cell.2014.07.044. ISSN   0092-8674. PMC   4151992 . PMID   25171412.
8. des Georges, Amedee; Dhote, Vidya; Kuhn, Lauriane; Hellen, Christopher U. T.; Pestova, Tatyana V.; Frank, Joachim; Hashem, Yaser (2015-09-07). "Structure of mammalian eIF3 in the context of the 43S preinitiation complex". Nature. 525 (7570). Springer Nature: 491–495. Bibcode:2015Natur.525..491D. doi:10.1038/nature14891. ISSN   0028-0836. PMC   4719162 . PMID   26344199.