Document Type

Article

Abstract

RNA sequences with the potential to form G-quadruplexes (rGQs) are widespread but largely unfolded in cells by unknown mechanisms. rGQ folding status is a critical regulator of RNA splicing and translation. We show that rGQs can be unfolded by SR proteins, SR-related proteins, and other Arg-rich proteins, including SRSF1, SRSF3, SRSF9, U1-70K, and U2AF1. The length and composition of Arg-rich regions are key determinants of this activity: Arg residues are the primary drivers, while acidic residues attenuate the unfolding activity. To unfold ARPC2 rGQ, at least 13 Arg residues are required. Our findings identify Arg-rich proteins as previously unrecognized, helicase-independent regulators of rGQ structures, with potential broad impacts on RNA processing that merit further investigation.

Digital Object Identifier (DOI)

https://doi.org/10.1002/1873-3468.70274

Rights

© 2026 The Author(s). FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

APA Citation

De Silva, N. I. U., Kunwar, P., Rifat Rahman, M. I., Kwao, J. K., Lehman, N., Zhang, Z., Paul, T., Cheng, C., Truex, N., Lee, H., & Zhang, J. (2026). Sequence determinants of RNA G‐quadruplex unfolding by Arg‐rich regions. FEBS Letters, 600(9), 1373–1385.https://doi.org/10.1002/1873-3468.70274

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