The 43S preinitiation complex (43S PIC) is a ribonucleoprotein complex that exists during an early step of

eukaryotic translation Eukaryotic translation is the biological process by which messenger RNA is translated into proteins in eukaryotes. It consists of four phases: gene translation, elongation, termination, and recapping. Initiation Translation initiation is the pr ...

initiation. The 43S PIC contains the small ribosomal subunit (40S) bound by the initiation factors eIF1,

eIF1A Eukaryotic translation initiation factor 1A, X-chromosomal (eIF1A) is a protein that in humans is encoded by the ''EIF1AX'' gene. This gene encodes an essential eukaryotic translation initiation factor. The protein is a component of the 43S pre-in ...

eIF3 Eukaryotic initiation factor 3 (eIF3) is a multiprotein complex that functions during the initiation phase of eukaryotic translation. It is essential for most forms of cap-dependent and cap-independent translation initiation. In humans, eIF3 co ...

, and the

eIF2 Eukaryotic Initiation Factor 2 (eIF2) is an eukaryotic initiation factor. It is required for most forms of eukaryotic translation initiation. eIF2 mediates the binding of tRNAiMet to the ribosome in a GTP-dependent manner. eIF2 is a heterotrimer c ...

-Met-

tRNA Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ...

_i^Met-GTP ternary complex (eIF2-TC).

Function

The 43S is an important intermediate complex during cap-dependent translation initiation. 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 Eukaryotic initiation factor 4F (eIF4F) is a heterotrimeric protein complex that binds the 5' cap of messenger RNAs (mRNAs) to promote eukaryotic translation initiation. The eIF4F complex is composed of three non-identical subunits: the DEAD-b ...

complex. The 43S PIC then "scans" in the 5' --> 3' direction along the mRNA in an ATP-dependent fashion (via

eIF4A The eukaryotic initiation factor-4A (eIF4A) family consists of 3 closely related proteins EIF4A1, EIF4A2, and EIF4A3. These factors are required for the binding of mRNA to 40S ribosomal subunits. In addition these proteins are helicases that ...

and/or other RNA

helicase Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separatin ...

s such as Ded1/DDX3 and

DHX29 DExH-box helicase 29 (DHX29) is a 155 kDa protein that in humans is encoded by the DHX29 gene. Function This gene encodes a member of the DEAH (Asp-Glu-Ala-His) subfamily of proteins, part of the DEAD (Asp-Glu-Ala-Asp) box family of RNA helic ...

) 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 The P-site (for peptidyl) is the second binding site for tRNA in the ribosome. The other two sites are the A-site (aminoacyl), which is the first binding site in the ribosome, and the E-site (exit), the third. During protein translation, the 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 Cryogenic electron microscopy (cryo-EM) is a cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample so ...

cross-link In chemistry and biology a cross-link is a bond or a short sequence of bonds that links one polymer chain to another. These links may take the form of covalent bonds or ionic bonds and the polymers can be either synthetic polymers or natural ...

ing, and the structural characterization of individual components, has led to models for the complex organization.

References

{{DEFAULTSORT:Eukaryotic Translation Molecular biology Gene expression RNA-binding proteins Protein biosynthesis Protein complexes

Function

Structure

See also

References