Eukaryotic initiation factor 4A-III (EIF4A3), a DEAD-box helicase, is present in eukaryotes and is expressed in the human body . Danio rerio, also known as zebrafish, is a common model organism in biological research. Recombinant EIF4A3 is produced using genetic engineering techniques, allowing for detailed studies of its function and interactions. EIF4A3 plays a role in RNA metabolism by participating in the exon junction complex (EJC) to control mRNA splicing and monitor mRNA quality before translation .
EIF4A3 consists of 411 amino acids, featuring a DEAD-box motif at positions 187–190 and a Q motif at positions 38-60 . The protein also contains an ATP-dependent helicase motif between amino acids 69–239 and a C-terminal helicase motif between amino acids 250-411 . The amino acid sequence of EIF4A3 is similar to that of human initiation factors EIF4A1 and EIF4A2 .
EIF4A3 is a core component of the exon junction complex (EJC) . The EJC is a multi-protein complex that influences post-transcriptional gene regulation by controlling precursor mRNA splicing . EIF4A3 binds to spliced mRNAs and regulates their splicing by recruiting peripheral proteins, affecting mRNA transportation, localization, translation, and nonsense-mediated mRNA decay (NMD) .
The EJC consists of four core proteins: EIF4A3, MAGOH, RBM8A, and CASC3 . After mRNA splicing, CASC3 binds to EIF4A3 to form the EJC tetramer . EIF4A3 interacts with the MAGOH-RBM8A dimer to prevent conformational changes, which forms a trimeric pre-EJC and provides a binding platform for other EJC components .
Under normal growth conditions, EIF4A-III has a general nucleoplasmic distribution but localizes to the nucleolus and nuclear splicing speckles under hypoxia stress conditions . The subnuclear localization of EIF4A-III is dynamic, and its presence in different regions of the nucleus may reflect different stages of EJC assembly and interactions with mRNA targets .
EIF4A3 binds to single-stranded RNA (ssRNA) in an ATP-dependent manner . The binding of the MAGOH–Y14 dimer inhibits ATP hydrolysis, which keeps EIF4A3 tightly associated with ssRNA .
EIF4A3 is implicated in tumor growth in cancers such as glioblastoma, hepatocellular carcinoma, pancreatic cancer, and ovarian cancer . EIF4A3 is recruited by long non-coding RNAs to regulate the expression of certain proteins in tumors .
| Feature | Description |
|---|---|
| Name | Eukaryotic initiation factor 4A-III (eIF4A3) |
| Organism | Danio rerio (Zebrafish) |
| Amino Acid Count | 411 |
| Motifs | DEAD-box motif (187–190), Q motif (38-60), ATP-dependent helicase motif (69–239), C-terminal helicase motif (250-411) |
| Function | Regulates mRNA splicing, monitors mRNA quality, influences mRNA transport, localization, translation, and NMD |
| Complex | Core component of the exon junction complex (EJC) |
| Interactions | MAGOH, RBM8A, CASC3, Aly/REF, Y14 |
| Subcellular Localization | Nucleoplasm, nucleolus, nuclear speckles |
| Role in Disease | Promotes tumor growth in multiple human cancers |