Eukaryotic Translation Initiation Factor 4A3 (EIF4A3) is a crucial protein involved in the initiation of translation in eukaryotic cells. It is a member of the DEAD-box protein family, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD). These proteins are putative RNA helicases, playing significant roles in various cellular processes that involve the alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly .
EIF4A3 is an ATP-dependent RNA helicase that unwinds RNA secondary structures, facilitating the binding of ribosomes to mRNA. This process is essential for the initiation of translation. The protein is highly similar in amino acid sequence to other members of the DEAD-box protein family, such as eIF4AI and eIF4AII .
EIF4A3 is a nuclear matrix protein and a core component of the exon junction complex (EJC). It participates in post-transcriptional gene regulation by promoting EJC control of precursor mRNA splicing, thus influencing nonsense-mediated mRNA decay . Additionally, EIF4A3 maintains the expression of significant selenoproteins, including phospholipid hydroperoxide glutathione peroxidase and thioredoxin reductase 1 .
Several studies have shown that EIF4A3 is highly expressed in various human cancers, such as glioblastoma, hepatocellular carcinoma, pancreatic cancer, and ovarian cancer . It can be recruited by long non-coding RNAs to stabilize proteins and promote tumorigenesis. The overexpression of EIF4A3 has been associated with tumor growth and progression, making it a potential target for cancer therapy .
Given its involvement in critical cellular processes and its overexpression in tumors, EIF4A3 is being studied as a potential diagnostic biomarker, therapeutic target, and prognosis indicator for various cancers . Understanding the molecular mechanisms underlying EIF4A3’s functions and its interactions with other proteins could provide new insights into cancer treatment strategies.