A quantitative model predicts how m6A reshapes the kinetic landscape of nucleic acid hybridization and conformational transitions

Bei Liu, Honglue Shi, Atul Rangadurai, Felix Nussbaumer, Chia-Chieh Chu, Kevin Andreas Erharter, David A. Case, Christoph Kreutz and Hashim M. Al-Hashimi ()
Additional contact information
Bei Liu: Duke University School of Medicine
Honglue Shi: Duke University
Atul Rangadurai: Duke University School of Medicine
Felix Nussbaumer: University of Innsbruck
Chia-Chieh Chu: Duke University School of Medicine
Kevin Andreas Erharter: University of Innsbruck
David A. Case: Rutgers University
Christoph Kreutz: University of Innsbruck
Hashim M. Al-Hashimi: Duke University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: ABSTRACT N6-methyladenosine (m6A) is a post-transcriptional modification that controls gene expression by recruiting proteins to RNA sites. The modification also slows biochemical processes through mechanisms that are not understood. Using temperature-dependent (20°C–65°C) NMR relaxation dispersion, we show that m6A pairs with uridine with the methylamino group in the anti conformation to form a Watson-Crick base pair that transiently exchanges on the millisecond timescale with a singly hydrogen-bonded low-populated (1%) mismatch-like conformation in which the methylamino group is syn. This ability to rapidly interchange between Watson-Crick or mismatch-like forms, combined with different syn:anti isomer preferences when paired (~1:100) versus unpaired (~10:1), explains how m6A robustly slows duplex annealing without affecting melting at elevated temperatures via two pathways in which isomerization occurs before or after duplex annealing. Our model quantitatively predicts how m6A reshapes the kinetic landscape of nucleic acid hybridization and conformational transitions, and provides an explanation for why the modification robustly slows diverse cellular processes.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25253-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25253-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25253-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().