A methylation-dependent reader couples arginine methylation to S6K2 signaling in vivo.

Authors

Yalong Wang, Bin Liu, Rongjie Fu, Wei He, Daniel J McGrail, Han Xu, Mark T Bedford

Published in

Science advances. Volume 12. Issue 43. Pages eaei1547. Oct 23, 2026. Epub Oct 23, 2026.

Abstract

Arginine methylation regulates diverse cellular processes, yet how methyl-arginine reader proteins couple this modification to kinase signaling in vivo remains poorly defined. Here, we identify staphylococcal nuclease and Tudor domain containing 1 (SND1) as a pancreas-enriched effector that links symmetric dimethylarginine (SDMA) recognition to S6 kinase 2 (S6K2) activation. Disruption of SDMA-mediated binding by a point mutation in the SND1 Tudor domain markedly diminishes ribosomal protein S6 (S6) phosphorylation in the pancreas. Mechanistically, SND1 engages SDMA-modified arginines within the carboxyl-terminal glycine-arginine-rich (GAR) motif of S6K2 and promotes S6K2-dependent S6 phosphorylation. Mice harboring lysine substitutions at these GAR arginines (S6k2 RK) phenocopy Snd1 Tudor-mutant (Snd1 knock-in) animals, exhibiting impaired pancreatic S6 phosphorylation. Transcriptomic analyses reveal extensive overlap in dysregulated pathways between Snd1 and S6k2 mutant pancreata, supporting a shared signaling cascade. Together, these findings establish a methylation-dependent reader-kinase axis that links protein arginine methyltransferase 5-catalyzed arginine methylation to tissue-specific control of ribosome signaling and cellular stress adaptation.

PMID:
42913003
Bibliographic data and abstract were imported from PubMed on 24 Oct 2026.

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