Salt-Dependent Self-Association of Trinucleotide Repeat RNA Sequences

Maity, Hiranmay; Nguyen, Hung T.; Hori, Naoto; Thirumalai, D.

Abstract

Repeat RNA sequences self-associate to form condensates. Simulations of a coarse-grained single-interaction site model for (CAG)n (n = 30 and 31) show that the salt-dependent free energy gap, ΔGS, between the ground (perfect hairpin) and the excited state (slipped hairpin (SH) with one CAG overhang) of the monomer for (n even) is the primary factor that determines the rates and yield of self-assembly. For odd n, the free energy (GS) of the ground state, which is an SH, is used to predict the self-association kinetics. As the monovalent salt concentration, CS, increases, ΔGS and GS increase, which decreases the rates of dimer formation. In contrast, ΔGS for shuffled sequences, with the same length and sequence composition as (CAG)31, is larger, which suppresses their propensities to aggregate. Although demonstrated explicitly for (CAG) polymers, the finding of inverse correlation between the free energy gap and RNA aggregation is general.

Citation

Maity, H., Nguyen, H. T., Hori, N., & Thirumalai, D. (2024). Salt-Dependent Self-Association of Trinucleotide Repeat RNA Sequences. Journal of Physical Chemistry Letters, 15(14), 3820–3827. https://doi.org/10.1021/acs.jpclett.3c03553

• Journal Article Type: Article
• Acceptance Date: Mar 25, 2024
• Online Publication Date: Apr 1, 2024
• Publication Date: Apr 11, 2024
• Deposit Date: Apr 2, 2024
• Publicly Available Date: Apr 2, 2025
• Journal: Journal of Physical Chemistry Letters
• Electronic ISSN: 1948-7185
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 14
• Pages: 3820–3827
• DOI: https://doi.org/10.1021/acs.jpclett.3c03553
• Keywords: RNA, Nucleic Acid Conformation, Trinucleotide Repeats, Sodium Chloride
• Public URL: https://nottingham-repository.worktribe.com/output/33026989
• Publisher URL: https://pubs.acs.org/doi/10.1021/acs.jpclett.3c03553