In eukaryotic cells, protein-coding genes are transcribed as pre-mRNA and undergo various mRNA processing. The TREX complex is loaded onto mRNA during splicing. Additionally, mRNA export receptors, Tap and p15 are recruited onto mRNA by the aid of TREX. These features of TREX make it possible that only mature mRNA is efficiently exported to cytoplasm. UAP56, one of the TREX subunit, functions as a key factor to form TREX complex. UAP56 homolog is conserved as a single gene from yeast to fly. But in mammals, there is another homologous gene, URH49.

Our previous study revealed that URH49 form a novel AREX complex, which is a different complex from TREX. And each complex regulates the export of different subset of mRNAs. Thus we assumed that, “the mutation of UAP56 ancestral gene generated URH49 which form AREX complex during evolution. As a result, sophisticated diverse mRNA export regulation system is acquired in human.”

To test this hypothesis, we identified the region that define the different complex formation by UAP56 and URH49, and analyzed the relationship between complex formation and selective mRNA export activity.

We constructed chimera mutants and amino acid substitution mutants between UAP56 and URH49. The complex formations of these mutants were analyzed by immune-precipitation. Specific amino acid exchange resulted in the exchange of complex formation. This result indicates that minimum portions of these proteins are the determination of the complex formation. Additionally we evaluate the selective mRNA export activities of these mutants by functional complementation experiment.

Consequently, mutants that formed TREX complex showed UAP56 specific mRNA export activity, others that formed AREX complex exhibit URH49 specific activity. These results suggest that TREX and AREX complex formations are correlated with UAP56 and URH49 selective mRNA export, respectively.

Currently, we are going to attempt to reveal the recognition mechanism of different subset of mRNAs by UAP56 and URH49.