PANAD/C7orf25 interacts with NXF1 to promote CDK6 mRNA nuclear export and G1/S transition

Nuclear export factor 1 (NXF1) exerts mRNA transporter activity via binding to adaptors. We aimed to identify new NXF1 adaptors, and found that the R122/E125/G133/D139 amino acid residues of C7orf25 interacted with the Q20/K22/K23 residues in the RBD domain of NXF1, which disrupted the intramolecular interaction between the RBD and NTF2L domains of NXF1, consequently enhancing the binding of NXF1 to target mRNAs and promoting mRNA nuclear export. Furthermore, C7orf25 accelerated the G1/S transition and promoted tumor cell growth via interacting with NXF1 to promote nuclear export of CDK6 mRNA. The levels of C7orf25, NXF1, and CDK6 proteins were elevated in human hepatocellular carcinomas, and high C7orf25 levels were associated with worse survival. These findings identify C7orf25, which we named PANAD (Proliferation-Associated NXF1 Adaptor), as a novel NXF1-interacting adaptor and disclose the crucial roles of PANAD/C7orf25 in mRNA nuclear export and tumor growth, which provides potential target for cancer therapy.