eIF3 is a large translation initiation complex with 10 to 13 different subunits. eIF3A, eIF3B, eIF3C, eIF3E, eIF3F, and eIF3H are the core subunits critical for the function of this complex. eIF3 physically interacts with eIF4G, which may be responsible for the association of the 40S ribosomal subunit with mRNA. eIF3 also stabilizes the binding of Met-tRNAf.eIF2.GTP to the 40S ribosomal subunit and helps keep the integrity of the resulting complex upon addition of the 60S ribosomal subunit. Studies have shown that mTOR interacts with eIF3 directly. When cells are stimulated by hormones or mitogenic signals, mTOR binds to the eIF3 complex and phosphorylates S6K1. This process results in the dissociation of S6K1 from eIF3 and S6K1 activation. The activated S6K1 then phosphorylates its downstream targets including ribosomal protein S6 and eIF4B, resulting in stimulation of translation. Further findings demonstrated that activated mTOR signaling induces the association of eIF3 with eIF4G upon stimulation with insulin.
Eukaryotic initiation factor 4A (eIF4A) has an essential role in the binding of mRNA to the 43S preinitiation complex when protein synthesisbegins, as eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the smallribosomal subunit, and subsequent scanning for the initiator codon.
Functions in close association with EIF4-F and EIF4-A. cRequired for the binding of mRNA to ribosomes. Binds near the 5'-terminal cap of mRNA in presence of EIF-4F and ATP. Promotes the ATPase activity and the ATP-dependent RNA unwinding activity of both EIF4-A and EIF4-F.,similarity:Contains 1 RRM (RNA recognition motif) domain.,subunit:Self-associates and interacts with EIF3 p170 subunit.
EIF4B (eukaryotic translation initiation factor 4B) is a protein-coding gene. GO annotations related to this gene include RNA binding and translation initiation factor activity. An important paralog of this gene is EIF4H.
The protein encoded by this gene is a component of the eukaryotic translation initiation factor 4F complex, which recognizes the 7-methylguanosine cap structure at the 5' end of messenger RNAs. The encoded protein aids in translation initiation by recruiting ribosomes to the 5'-cap structure. Association of this protein with the 4F complex is the rate-limiting step in translation initiation. This gene acts as a proto-oncogene, and its expression and activation is associated with transformation and tumorigenesis. Several pseudogenes of this gene are found on other chromosomes. Alternative splicing results in multiple transcript variants.
The initiation of translation is an important biological event and a variety of factors contribute to this process. Members of the eIF4 translation initiation factor family bind to the 5' m7GTP mRNA cap and unwind the mRNA secondary structure. The amino-terminal portion of eIF4G physically associates with eIF4E to stimulate the binding of eIF4E to the mRNA cap structure. eIF4G also interacts with eIF3 and eIF4A and serves as an adaptor molecule in the eIF4 complex. Moreover, eIF4G plays a role in internal ribosomal entry site (IRES)-mediated initiation of translation. The eIF4G family includes eIF4G1 (eIF4GI), eIF4G2 (p97, DAP5 or NAT1), and eIF4G3 (eIF4GII). These factors share a homologous sequence that provides for interaction with initiation factors eIF3 and eIF4A. Both eIF4G1 and eIF4G3 are involved in cap-dependent translation, while eIF4G2 plays a role in IRES-mediated translation of some genes during cell stress.
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