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

ABSTRACT: Processing (P)-bodies are non-membrane cellular structures containing proteins involved in mRNA decay. 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. The deletion of KH-1, both KHDs, or mutation in the existing non-canonical GXXG motifs in KHDs abolish N4BP1’s interaction with EDC4, indicating that both domains are mandatory for interaction with EDC4.

ORGANISM(S): Homo sapiens

PROVIDER: GSE282898 | GEO | 2026/09/18

REPOSITORIES: GEO

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

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