Eukaryotic initiation factor 4A-III (EIF4A3)

Eukaryotic initiation factor 4A-III (EIF4A3) is a central member of the DEAD-box RNA helicase family, recognized as the core RNA-binding component of the exon junction complex (EJC)[1][5][7]. EIF4A3 binds to mRNAs upstream of exon-exon boundaries after splicing in the nucleus, facilitating processes such as nonsense-mediated mRNA decay, mRNA export, and surveillance[1][4][5][7]. It acts as an essential scaffold for EJC assembly and for recruiting factors mediating RNA stability, transport, and translation regulation[1][7]. EIF4A3 plays critical roles in cell cycle control, stem cell pluripotency, ribosomal RNA (rRNA) processing, and tumor cell growth[2][3][6][7]. Overexpression of EIF4A3 has been linked to increased tumor cell proliferation and poor prognosis in various cancers; it is considered a tractable vulnerability in high ribosome biogenesis tumors[6]. EIF4A3 is also hijacked by certain viruses, such as influenza A, to promote viral RNA splicing and export[4]. Therapeutic inhibition of EIF4A3 is currently experimental and poses challenges due to the enzyme’s essential housekeeping roles in normal proliferative cells[7].

Other names

Eukaryotic initiation factor 4A-IIIDEAD box protein 48ATP-dependent RNA helicase DDX48eIF4A-IIIDDX48KIAA0111NMP 265hNMP 265Fal1Nuclear matrix protein 265NUK-34RCPSMUK34

Inhibition of RNA helicase activity; Inhibition of exon junction complex deposition/function; Disruption of nonsense-mediated mRNA decay; Modulation of RNA stress granule dynamics