HGNC Approved Gene Symbol: EIF4B
Cytogenetic location: 12q13.13 Genomic coordinates (GRCh38): 12:53,006,456-53,042,215 (from NCBI)
Eukaryotic translation initiation factor 4B (eIF4B) facilitates the binding of mRNA to the 43S preinitiation complex, which consists of the 40S ribosomal subunit bound to a ternary complex of eIF2, GTP, and Met-tRNA stabilized by eIF3 (see p66; 603915). eIF4F, a heterotrimeric protein, binds to the mRNA cap structure and, in combination with eIF4B, is thought to unwind the secondary structure in the 5-prime untranslated region of the mRNA to facilitate ribosome binding. Besides its RNA-binding activity, eIF4B stimulates the ATPase and RNA helicase activities of eIF4A (602641), one component of eIF4F (Methot et al. (1996)).
By screening a fetal liver library with degenerate oligonucleotide probes based on the partial protein sequence of HeLa cell eIF4B, Milburn et al. (1990) isolated a partial cDNA encoding human eIF4B. They used the partial cDNA to screen an osteosarcoma library and recovered additional cDNAs corresponding to 2 distinct transcripts that had the same coding region but 3-prime ends of different lengths. Northern blot analysis revealed that eIF4B is expressed as 4.4- and 2.3-kb mRNAs in human cell lines. Milburn et al. (1990) determined that the 2 mRNAs differ by alternate utilization of polyadenylation signals. The predicted 611-amino acid eIF4B protein contains a consensus RNA-binding site (RNP-CS) near the N terminus, a central domain rich in aspartic acid, arginine, tyrosine, and glycine (DRYG-rich), and a C-terminal region with a large number of polar residues. The authors suggested that the highly polar DRYG region may account for the aberrant migration of eIF4B by SDS-PAGE: the factor has a predicted molecular weight of 70 kD, but an apparent molecular weight of 80 kD. Overexpression of eIF4B in mammalian cells inhibited translation. Southern blot analysis suggested that there are multiple eIF4B genes or pseudogenes in the human genome.
Methot et al. (1994) determined that both the RNA recognition motif (RRM)/RNP-CS and a C-terminal RNA-binding region are essential for eIF4B function. Methot et al. (1996) demonstrated that the DRYG domain of eIF4B mediates self-association and interaction with the p170 (602039) subunit of eIF3. They proposed that eIF4B serves as a bridge between the mRNA and the 40S ribosomal subunit, by binding both mRNA and 18S ribosomal RNA. The direct interaction between eIF4B and eIF3, which is present on the 43S preinitiation complex prior to mRNA binding, provides an additional link between the mRNA and the ribosome.
Using a single-molecule assay, Garcia-Garcia et al. (2015) found that eiF4A functions as an adenosine triphosphate-dependent processive helicase when complexed with 2 accessory proteins, eIF4G (600495) and eIf4B. Translocation occurred in discrete steps of 11 +/- 2 basepairs, irrespective of the accessory factor combination. Garcia-Garcia et al. (2015) concluded that their findings supported a memoryless stepwise mechanism for translation initiation and suggested that similar factor-dependent processivity may be shared by other members of the DEAD-box helicase family.
Garcia-Garcia, C., Frieda, K. L., Feoktistova, K., Fraser, C. S., Block, S. M. Factor-dependent processivity in human eIF4A DEAD-box helicase. Science 348: 1486-1488, 2015. [PubMed: 26113725] [Full Text: https://doi.org/10.1126/science.aaa5089]
Methot, N., Pause, A., Hershey, J. W., Sonenberg, N. The translation initiation factor eIF-4B contains an RNA-binding region that is distinct and independent from its ribonucleoprotein consensus sequence. Molec. Cell. Biol. 14: 2307-2316, 1994. [PubMed: 8139536] [Full Text: https://doi.org/10.1128/mcb.14.4.2307-2316.1994]
Methot, N., Song, M. S., Sonenberg, N. A region rich in aspartic acid, arginine, tyrosine, and glycine (DRYG) mediates eukaryotic initiation factor 4B (eIF4B) self-association and interaction with eIF3. Molec. Cell. Biol. 16: 5328-5334, 1996. [PubMed: 8816444] [Full Text: https://doi.org/10.1128/MCB.16.10.5328]
Milburn, S. C., Hershey, J. W. B., Davies, M. V., Kelleher, K., Kaufman, R. J. Cloning and expression of eukaryotic initiation factor 4B cDNA: sequence determination identifies a common RNA recognition motif. EMBO J. 9: 2783-2790, 1990. [PubMed: 2390971] [Full Text: https://doi.org/10.1002/j.1460-2075.1990.tb07466.x]