Eukaryotic initiation factor 4F (eIF4F) is a heterotrimeric

protein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multidomain enzymes, in which multiple active site, catalytic domains are found in a single polypeptide chain. ...

that binds 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 messenger RNAs (mRNAs) to promote

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 eIF4F complex is composed of three non-identical subunits: the DEAD-box RNA helicase

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 ...

, the cap-binding protein

eIF4E Eukaryotic translation initiation factor 4E, also known as eIF4E, is a protein in humans encoded by the ''EIF4E'' gene. eIF4E plays a central role in translation initiation and is involved in regulating protein synthesis. Its activity influences ...

, and the large "scaffold" protein

eIF4G Eukaryotic translation initiation factor 4 G (eIF4G) is a protein involved in eukaryotic translation initiation and is a component of the eIF4F cap-binding complex. Orthologs of eIF4G have been studied in multiple species, including humans, yeast ...

. The mammalian eIF4F complex was first described in 1983, and has been a major area of study into the molecular mechanisms of cap-dependent translation initiation ever since.

Function

eIF4F is important for recruiting the small ribosomal subunit (40S) to the

of mRNAs during cap-dependent translation initiation. Components of the complex are also involved in cap-independent translation initiation; for instance, certain viral

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products ...

s cleave eIF4G to remove the eIF4E-binding region, thus inhibiting cap-dependent translation.

Structure

Structures of eIF4F components have been solved individually and as partial complexes by a variety of methods, but no complete structure of eIF4F is currently available.

Subunits

In mammals, the eIF4E•G•A trimeric complex can be directly purified from cells, while only the two subunit eIF4E•G can be purified from yeast cells. This suggests that the interaction between the eIF4A and eIF4G in yeast is not as stable.

binds the m⁷G

and the eIF4G scaffold, connecting the mRNA 5' terminus to a hub of other

initiation factor In molecular biology, initiation factors are proteins that bind to the small subunit of the ribosome during the initiation of Translation (genetics), translation, a part of protein biosynthesis. Initiation factors can interact with repressors to ...

s and mRNA. The interaction of eIF4G•A is thought to guide the formation of a single-stranded RNA landing pad for the 43S preinitiation complex (43S PIC) via eIF4A's RNA helicase activity. The eIF4F proteins interact with a number of different binding partners, and there are multiple genetic isoforms of

, and

in the human genome. In mammals, eIF4F is bridged to the 40S ribosomal subunit by

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 ...

via

, while

budding yeast ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungal microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been ...

lacks this connection. Interactions between

and PABP are thought to mediate the circularization of mRNA particles, forming a "closed-loop" thought to stimulate translation. Approximate molecular weight for human proteins. In addition to the major proteins encompassing the eIF4F trimer, the eIF4F complex functionally interacts with proteins including eIF4B and eIF4H. The unusual isoform of eIF4G, eIF4G2 or DAP5, also appears to perform a non-canonical translation function.

Regulation

The

subunit of eIF4F is an important target of

mTOR The mammalian target of rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MTOR'' gene. ...

signaling through the eIF4E binding protein (4E-BP). Phosphorylation of 4E-BPs by mTOR prevents their binding to eIF4E, freeing eIF4E to bind eIF4G and participate in translation initiation.

References

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

Function

Structure

Subunits

Regulation

See also

References