EIF4G
| Initiation factor 4G | |
|---|---|
| Identifiers | |
| Symbol | IF4G |
| InterPro | IPR045208 |
Eukaryotic translation initiation factor 4 G (eIF4G) is a protein involved in
.)Across species, eIF4G strongly associates with eIF4E, the protein that directly binds the mRNA cap. Together with the RNA helicase protein eIF4A, these form the eIF4F complex.
Within the cell eIF4G is found primarily in the cytoplasm, usually bound to eIF4E; however, it is also found in the nucleus, where its function is unknown. It may have a role in nonsense-mediated decay.
History
eIF4G stands for eukaryotic initiation factor 4 gamma (typically gamma is now replaced by G in the literature). It was initially isolated by fractionation, found present in fraction 4 gamma, and was involved in eukaryotic translation initiation.
Binding partners
eIF4G has been found to associate with many other proteins besides those of the
In translation initiation
eIF4G is an important scaffold for the eIF4F complex and aids in recruiting the 40S ribosomal subunit to mRNA.
There are three mechanisms that the 40S ribosome can come to recognize the start codon: scanning, internal entry, and
eIF4G is an
In disease
eIF4G has been implicated in breast cancer. It appears in increased levels in certain types of breast cancer and increases production of mRNAs that contain IRESs; these mRNAs produce hypoxia- and stress-related proteins that encourage blood vessel invasion (which is important for tumorigenesis).
Role in aging
Regulation of translation initiation by eIF4G is vital for protein synthesis in developing organisms, for example yeast and nematodes. Deletion of eIF4G is lethal in yeast.[2] In the roundworm C. elegans, knockout of eIF4G leads to animals that cannot develop past the early larval stage (L2) of development.[3] The critical role of eIF4G in development appears to be reversed in adulthood, when eIF4G dysregulation negatively impacts lifespan and increases susceptibility to certain aging-related diseases (see eIF4G in diseases above). Inhibiting eIF4G during adulthood in C. elegans drastically extends lifespan, comparable to the lifespan increase exhibited during dietary restriction.[4] In addition, inhibiting eIF4G reduces overall protein translation, while preferentially translating mRNA of genes important for responding to stress and against those associated with growth and reproduction.[5] Thus eIF4G appears to control differential mRNA translation during periods or growth and stress, which may ultimately lead to age-related decline.
Importance in virology
As previously mentioned, eIF4G is bound by certain IRESs, which were initially discovered in viruses. Some viral IRESs directly bind eIF4G and co-opt it to gain access to the ribosome. Some cellular mRNAs also contain IRESs (including eIF4G itself).[6]
Some viral proteases cleave off part of eIF4G, that contains the eIF4E binding region. This has the effect of preventing most cellular mRNAs from binding eIF4G; however, a few cellular mRNAs with IRESs still translate under these conditions.
One example of an eIF4G binding site in a viral IRES is in the EMCV IRES (nucleotides 746–949).[7]