2'-O-Methylation can increase the abundance and lifetime of alternative RNA conformational states.
Nucleic Acids Res
; 48(21): 12365-12379, 2020 12 02.
Article
em En
| MEDLINE
| ID: mdl-33104789
ABSTRACT
2'-O-Methyl (Nm) is a highly abundant post-transcriptional RNA modification that plays important biological roles through mechanisms that are not entirely understood. There is evidence that Nm can alter the biological activities of RNAs by biasing the ribose sugar pucker equilibrium toward the C3'-endo conformation formed in canonical duplexes. However, little is known about how Nm might more broadly alter the dynamic ensembles of flexible RNAs containing bulges and internal loops. Here, using NMR and the HIV-1 transactivation response (TAR) element as a model system, we show that Nm preferentially stabilizes alternative secondary structures in which the Nm-modified nucleotides are paired, increasing both the abundance and lifetime of low-populated short-lived excited states by up to 10-fold. The extent of stabilization increased with number of Nm modifications and was also dependent on Mg2+. Through phi-value analysis, the Nm modification also provided rare insights into the structure of the transition state for conformational exchange. Our results suggest that Nm could alter the biological activities of Nm-modified RNAs by modulating their secondary structural ensembles as well as establish the utility of Nm as a tool for the discovery and characterization of RNA excited state conformations.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA Viral
/
Processamento Pós-Transcricional do RNA
/
Repetição Terminal Longa de HIV
/
Magnésio
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article