eIF4AIII

eIF4AIII, or eukaryotic initiation factor 4AIII, is a member of the DEAD-box RNA helicase family. It is a highly conserved protein found in most eukaryotes and is distinguished from other eIF4A family members by its primary involvement in RNA processing and surveillance rather than translation initiation.

In mature mRNA, eIF4AIII is a core component of the exon junction complex (EJC), which is deposited upstream of exon-exon junctions during splicing. It forms a stable core with MAGOH and RBM8A (also known as Y14), and the association of MLN51 (CASC3) with this complex further stabilizes the EJC. The EJC functions as a marker that influences mRNA export, localization, and surveillance mechanisms that monitor transcript integrity.

Mechanistically, eIF4AIII is a DEAD-box RNA helicase that hydrolyzes ATP to bind and remodel RNA. Within the EJC, interactions with MAGOH and RBM8A lock eIF4AIII in a closed, RNA-binding conformation, enabling the complex to associate with RNA near splice junctions. The EJC can be released when appropriate, allowing export to proceed and translation to occur.

Functionally, the EJC, including eIF4AIII, participates in nonsense-mediated decay (NMD) by providing positional information that the NMD machinery uses to distinguish premature stop codons. It also contributes to efficient mRNA export, cytoplasmic localization, and selective translation regulation for certain transcripts.

Evolutionarily, eIF4AIII is conserved across eukaryotes, reflecting its essential role in post-transcriptional gene regulation. Disruption of EJC components can impact development and gene expression, highlighting the importance of eIF4AIII in RNA metabolism.