E1F4E

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Template:PBB/1977 Eukaryotic translation initiation factor 4E, also known as eIF4E, is a protein which in humans is encoded by the eIF4E gene.[1][2]

Function

All eukaryotic cellular mRNAs are modified at their 5-prime ends with the 7-methyl-guanosine cap structure, m7GpppX (where X is any nucleotide). This structure is involved in several cellular processes including enhanced translational efficiency, splicing, mRNA stability, and RNA nuclear export. EIF4E is a eukaryotic translation initiation factor involved in directing ribosomes to the cap structure of mRNAs. It is a 24-kD polypeptide that exists as both a free form and as part of a multiprotein complex termed EIF4F. The EIF4E polypeptide is the rate-limiting component of the eukaryotic translation apparatus and is involved in the mRNA-ribosome binding step of eukaryotic protein synthesis. The other subunits of EIF4F are a 50-kD polypeptide, termed EIF4A, that possesses ATPase and RNA helicase activities, and a 220-kD polypeptide, EIF4G.[3][4]

eIF4E's function is to bind an mRNA cap and ultimately bring it to the ribosome. eIF4E is part of the eIF4F pre-initiation complex; which is made up of eIF4E, and eIF4G (eIF4F is sometimes considered to have additional protein components). Almost all cellular proteins require eIF4E in order to be translated into protein. eIF4E binds the first nucleotide on the 5' end of an mRNA molecule (known as the cap): a 7 methyl guanosine (m7G). It sandwiches m7G between 2 tryptophan residues, and other amino acids are involved in the binding.

Some viruses cut eIF4G in such a way that the eIF4E binding site is removed and the virus is able to translate its proteins without eIF4E. Also some cellular proteins, most notably heat shock proteins, don't require eIF4E in order to be translated. Both viruses and cellular proteins achieve this through an IRES structure in the RNA.

FMRP Represses Translation through EIF4E Binding

Fragile X mental retardation protein (FMRP) acts to regulate translation of specific mRNAs through its binding of eIF4E. FMRP acts by binding CYFIP1, which directly binds eIF4e at a domain that is structurally similar to those found in 4E-BPs, including . The FMRP/CYFIP1 complex binds in such a way as to prevent the eIF4E-eIF4G interaction which is necessary for translation to occur. The FMRP/CYFIP1/eIF4E interaction is strengthened by the presence of mRNAs. In particular, BC1 RNA allows for the optimal interaction between FMRP and CYFIP1.[5] RNA-BC1 is a non-translatable, dendritic mRNA, which binds FMRP to allow its association with the specific target mRNA. It is suggested that BC1 may function to regulate FMRP and mRNA interactions at synapses by its recruitment of FMRP to the appropriate mRNA. [6] It is hypothesized that FMRP may recruit CYFIP1 to specific mRNAs in order to repress translation. The FMRP-CYFIP1 translational inhibitor is regulated by stimulation of neurons. Increased synaptic stimulation resulted in the dissociation of eIF4E and CYFIP1, allowing for the initiation of translation.[7]

Interactions

EIF4E has been shown to interact with EIF4A1,[8][9] EIF4EBP3,[10][11] EIF4EBP1,[8][9][12][13][14][15][16][17][18][19][20][21][22] EIF4EBP2,[13][23] Eukaryotic translation initiation factor 4 gamma,[9][13][18][24][25] EIF4G2[26] and EIF4ENIF1.[27]

See also

References

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External links

Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.Template:Initiation factors


pl:EIF-4E zh:真核起始因子4E