Eukaryotic initiation factor 4A1 (eIF4A1) (eIF4A1)

Eukaryotic initiation factor 4A1 (eIF4A1) is an ATP-dependent RNA helicase and a central component of the eIF4F translation initiation complex, which also includes the cap-binding protein eIF4E and the scaffold protein eIF4G (UniProt, Wikipedia). Its primary biological function is to unwind stable secondary structures in the 5' untranslated regions (UTRs) of mRNAs, a process essential for the recruitment and scanning of the 43S pre-initiation complex to locate the start codon (NIH, PMC10666758). In many human malignancies, eIF4A1 is significantly overexpressed and selectively promotes the translation of mRNAs with complex 5' UTRs, many of which encode potent oncoproteins like MYC, BCL2, and CDK6 (MDPI, Cancers 2023). This dependency makes eIF4A1 an attractive therapeutic target, particularly in cancers driven by these structured mRNAs. Small molecule inhibitors, such as the rocaglate Zotatifin, work by clamping eIF4A1 onto polypurine sequences in the RNA, effectively blocking its helicase activity and inhibiting the synthesis of key drivers of tumor growth and survival (eFfector Therapeutics). Beyond oncology, eIF4A1 has been implicated in viral replication and myocardial ischemia-reperfusion injury, suggesting broader clinical relevance (NIH, PMC8534148).

Other names

DDX2AeIF4AeIF-4A-IATP-dependent RNA helicase eIF4A-1Eukaryotic translation initiation factor 4A1

Inhibition of RNA helicase activity by stabilizing the eIF4A-RNA complex (rocaglates) or blocking ATPase activity (hippuristanol), preventing the unwinding of structured 5' UTRs and inhibiting translation of pro-oncogenic mRNAs.