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

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

10.64898/2026.06.30.735655 · was preprinted

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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.

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biorxiv v1 2026-07-09 source ↗

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