Regulation of RNA maturation by the family of human G-patch proteins

Authors

Memet, I., Kanwal, N., Ritchie, A., Krogh, N., Lenz, C., Oudelaar, A. M., Nielsen, H., Urlaub, H., Herzel, L., Bohnsack, K. E., Bohnsack, M. T.

Abstract

The family of human G-patch proteins comprises more than 20 members, each characterized by a glycine-rich G-patch implicated in mediating interactions with RNA helicases. Here, we systematically identify the cognate RNA helicase of each G-patch protein, highlighting the association of DHX15 with a network of 20 G-patch cofactors. DHX35 and GPATCH1 represent a unique G-patch protein-RNA helicase pair, and we uncover a regulatory circuit between these partners. Comprehensive in vitro analyses of ATPase activity and RNA binding identify distinguishing features of DHX15- and non-DHX15-associated G-patch proteins, and demonstrate the roles of most G-patch proteins as bona fide stimulatory cofactors of DHX15. RNA interactome analyses of each G-patch protein and complementary transcriptome-wide alternative splicing analyses in cells lacking a G-patch protein reveal distinct modes of regulation of mRNA maturation by different G-patch proteins. For example, ZGPAT affects splicing indirectly through its requirement for efficient 2'-O-methylation of snRNAs, GPATCH8 exemplifies DHX15-associated alternative splicing modulation, whereas SUGP2 suppresses splicing in an RNA helicase-independent manner via direct binding to pre-mRNA introns.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 10 Jul 2026.

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