Sequence determinants of RNA G‐quadruplex unfolding by Arg‐rich regions

FEBS Letters 2026 Open access

Read full text
Authors: Naiduwadura Ivon Upekala De Silva, Puspa Kunwar, Md Ibnul Rifat Rahman, Joanna Koryo Kwao, Nathan Lehman, Zihan Zhang, Trenton Paul, Claire Cheng, Nicholas L. Truex, Hui‐Ting Lee, Jun Zhang
DOI: 10.1002/1873-3468.70274
Cited by: 2
References: 30

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.

Fields of Study & Subjects

RNA Research and Splicing DNA and Nucleic Acid Chemistry RNA and protein synthesis mechanisms

Publication details

Journal / source
FEBS Letters
Publisher
Wiley
Volume
600
Issue
9
Pages
1373–1385
Publication date
9 January 2026
Language
EN