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 Translation (biology), translated into proteins in eukaryotes. It consists of four phases: initiation, elongation, termination, and recapping. Initiation Translation init ...

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

eIF1 Eukaryotic translation initiation factor 1 (eIF1) is a protein that in humans is encoded by the ''EIF1'' gene. It is related to yeast SUI1. eIF1 interacts with the eukaryotic small ( 40S) ribosomal subunit and eIF3, and is a component of the 43S ...

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-i ...

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 Eukaryotic translation#Cap-dependent initiation, cap-dependent and Eukaryotic ...

, and the

eIF2 Eukaryotic Initiation Factor 2 (eIF2) is a 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 ...

-Met-

tRNA Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...

_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 In molecular biology, the five-prime cap (5′ cap) is a specially altered nucleotide on the 5′ end of some primary transcripts such as precursor messenger RNA. This process, known as mRNA capping, is highly regulated and vital in the creation ...

of eukaryotic

messenger RNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...

s (mRNAs) by the

eIF4F Eukaryotic initiation factor 4F (eIF4F) is a heterotrimeric protein complex that binds the Five-prime cap, 5' cap of Messenger RNA, messenger RNAs (mRNAs) to promote eukaryotic translation initiation. The eIF4F complex is composed of three non-i ...

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 Messenger RNA, mRNA to 40S ribosome, ribosomal subunits. In addition these prot ...

and/or other RNA

helicase Helicases are a class of enzymes that are 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 double helix, separating the two hybridized ...

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-sit ...

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 transmission electron microscopy technique applied to samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An ...

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