N4BP1 RNase uses tandem KH domains to associate with EDC4 and mRNA decapping factors in P-bodies

The enhancer of mRNA decapping protein 4 (EDC4) acts as a scaffold for the formation of the mRNA decapping complex in P-bodies. We show that NEDD4-binding partner-1 (N4BP1) interacts with EDC4 and with the DCP1A and XRN1 proteins involved in the hydrolysis of the mRNA 5′-cap structure in P-bodies.

The two tandem KH domains (KHDs), KH-1 and KH-2, present in N4BP1 are essential for its interaction with EDC4. A crystal structure of the tandem KHDs revealed a typical type-I KH topology for both KH domains of N4BP1, and assembly into a globular fold. The N4BP1 KHDs lack the canonical GXXG motif necessary for interaction with single-stranded nucleic acids.