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

Piłat, Paweł, Garg, Ankur, Heinemann, Udo, Wilamowski, Mateusz, Jura, Jolanta (September 2026) N4BP1 uses tandem KH domains to associate with EDC4 and mRNA decapping factors in P-bodies. Communications Biology, 9 (1). ISSN 2399-3642

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Abstract

Processing bodies (P-bodies) are cytoplasmic, non-membrane-bound structures involved in mRNA decay. EDC4 serves as a key scaffold for the decapping complex within P-bodies. Here, we demonstrate that N4BP1 interacts with EDC4, as well as with DCP1A, DCP2, and XRN1 - key components of 5′-cap hydrolysis. Endogenous N4BP1 colocalizes with EDC4 in P-bodies, requiring both of its KH domains. Structural analysis revealed that N4BP1 contains a type-I KH fold but lacks the canonical GXXG motif required for single-stranded RNA binding. Deletion or mutation of KH domains non-canonical GXXG motifs disrupts the N4BP1-EDC4 complex. N4BP1 reduces HIV-1 transcript levels independently of its P-body localization or association with decapping components, implying the involvement of other host factors in regulating viral mRNAs. Similarly, for N4PB1-dependend negative regulation of endogenous transcripts in HaCaT keratinocytes, EDC4 is not essential. For both HIV-1 and endogenous transcripts, the reduction is associated with the activity of the NYN domain

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
CSHL Authors:	Garg, Ankur
Communities:	CSHL labs > Joshua-Tor lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	17 September 2026
Date Deposited:	21 Sep 2026 13:19
Last Modified:	21 Sep 2026 13:19
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/42317

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