Alternative titles; symbols
HGNC Approved Gene Symbol: EIF3H
Cytogenetic location: 8q23.3-q24.11 Genomic coordinates (GRCh38): 8:116,642,130-116,766,374 (from NCBI)
Eukaryotic initiation factor-3 (eIF3) is the largest of the eIFs and consists of at least 10 nonidentical subunits in mammals. See p66 (EIF3S7; 603915). By searching EST databases with the partial protein sequences of rabbit p66, p47 (603914), and p40, Asano et al. (1997) identified cDNAs encoding the human homologs. The predicted human p40 protein contains 352 amino acids. Sequence analysis revealed that the N-terminal halves of p40 and p47 are similar to each other and are related to the mouse Mov34 (see 157970) protein. Northern blot analysis revealed that p40 is expressed as a 1.3-kb mRNA.
Schmidt et al. (1999) determined that the EIF3S3 gene comprises 8 exons and is transcribed from telomere to centromere.
Using a library of endoribonuclease-prepared short interfering RNAs (esiRNAs), Kittler et al. (2004) identified 37 genes required for cell division, one of which was EIF3S3. These 37 genes included several splicing factors for which knockdown generates mitotic spindle defects. In addition, a putative nuclear-export terminator was found to speed up cell proliferation and mitotic progression after knockdown.
Choe et al. (2018) demonstrated that METTL3 (612472) enhances translation only when tethered to reporter mRNA at sites close to the stop codon, supporting a mechanism of mRNA looping for ribosome recycling and translational control. Electron microscopy revealed the topology of individual polyribosomes with single METTL3 foci in close proximity to 5-prime cap-binding proteins. Choe et al. (2018) identified a direct physical and functional interaction between METTL3 and EIF3H. METTL3 promotes translation of a large subset of oncogenic mRNAs, including bromodomain-containing protein-4 (BRD4; 608749), that is also N6-methyladenosine (m6A)-modified in human primary lung tumors. The METTL3-EIF3H interaction is required for enhanced translation, formation of densely packed polyribosomes, and oncogenic transformation. METTL3 depletion inhibits tumorigenicity and sensitizes lung cancer cells to BRD4 inhibition. Choe et al. (2018) concluded that these findings uncovered a mechanism of translation control that is based on mRNA looping.
Using ESTs, Schmidt et al. (1999) found that the EIF3S3 gene maps close to the distal border of the minimal critical region for type I trichorhinophalangeal syndrome (TRPS1; 190350) on 8q24.
Exclusion Studies
Because its location on chromosome 8q24 made EIF3S3 a candidate gene for TRPS1, Schmidt et al. (1999) searched for gene deletions and mutations in patients with TRPS1. No deletion could be detected in 32 unrelated patients with an apparently normal karyotype. Furthermore, sequence analysis of all exons in 15 unrelated patients did not reveal any point mutation.
Asano, K., Vornlocher, H.-P., Richter-Cook, N. J., Merrick, W. C., Hinnebusch, A. G., Hershey, J. W. B. Structure of cDNAs encoding human eukaryotic initiation factor 3 subunits: possible roles in DNA binding and macromolecular assembly. J. Biol. Chem. 272: 27042-27052, 1997. [PubMed: 9341143] [Full Text: https://doi.org/10.1074/jbc.272.43.27042]
Choe, J., Lin, S., Zhang, W., Liu, Q., Wang, L., Ramirez-Moya, J., Du, P., Kim, W., Tang, S., Sliz, P., Santisteban, P., George, R. E., Richards, W. G., Wong, K.-K., Locker, N., Slack, F. J., Gregory, R. I. mRNA circularization by METTL3-eIF3h enhances translation and promotes oncogenesis. Nature 561: 556-560, 2018. [PubMed: 30232453] [Full Text: https://doi.org/10.1038/s41586-018-0538-8]
Kittler, R., Putz, G., Pelletier, L., Poser, I., Heninger, A.-K., Drechsel, D., Fischer, S., Konstantinova, I., Habermann, B., Grabner, H., Yaspo, M.-L., Himmelbauer, H., Korn, B., Neugebauer, K., Pisabarro, M. T., Buchholz, F. An endoribonuclease-prepared siRNA screen in human cells identifies genes essential for cell division. Nature 432: 1036-1040, 2004. [PubMed: 15616564] [Full Text: https://doi.org/10.1038/nature03159]
Schmidt, O., von Holtum, D., Gross, S., Horsthemke, B., Ludecke, H.-J. The EIF3S3 gene encoding the p40 subunit of the translation initiation factor eIF3 has eight exons and maps to the Langer-Giedion syndrome chromosome region on 8q24, but is not the TRPS1 gene. Hum. Genet. 105: 662-664, 1999. [PubMed: 10647903] [Full Text: https://doi.org/10.1007/s004399900175]