eIF4A3 (F9X7Z) Rabbit Monoclonal Antibody #52960

The exon junction complex (EJC) plays a critical role in splicing, translation, mRNA localization, and nonsense-mediated decay (NMD). It is composed of four core proteins: eukaryotic initiation factor 4A3 (eIF4A3), Mago homolog (MAGOH), RBM8A or Y18, and metastatic lymph node 51 (MLN51) (1-4). The EJC proteins act as a binding platform for auxiliary factors that control mRNA export and NMD (5). RBM8A and MAGOH bind to key NMD factor UPF3B and dock around 20 nucleosides upstream of exon-exon junctions, which helps facilitate proper splicing and NMD functions (6-8). Ribosomes will determine whether NMD factors are needed when encountering a stop codon during translation. If EJCs exist downstream of the stop codon, the ribosome will recruit the SURF complex, and UPF1 phosphorylation will help facilitate the decay of prematurely terminated mRNAs (9,10). The EJC is also involved in the cell cycle as eIF4A3 is phosphorylated at Thr163 by CDK1 and CDK2, which inhibits NMD function and prevents complex formation (11,12). Aberrant RBM8A expression causes cell cycle dysfunction, while low MAGOH expression affects neurological development and proliferation (13,14). EJC members have been implicated in a wide array of diseases and cancers, including hepatocellular carcinoma, glioblastoma, and neurological disorders (15-17).

eIF4A3 specifically has been linked to many different cancers by facilitating the formation of a vast array of circular RNAs (circRNAs). These circRNAs often act in opposition to key miRNAs, resulting in a loss of checks and balances and tumorigenesis. eIF4A3-dependent circRNAs have been implicated in glioblastoma, triple-negative breast cancer, and gastric cancer among others (18-20). The critical role of eIF4A3 in global splicing, NMD, and cell cycle makes it an attractive target for selective inhibitors (21,22).