pH dependence of C•A, G•A and A•A mismatches in the stem of precursor microRNA-31

Anita Kotar; Sicong Ma; Sarah C Keane

doi:10.1016/j.bpc.2022.106763

pH dependence of C•A, G•A and A•A mismatches in the stem of precursor microRNA-31

Biophys Chem. 2022 Apr:283:106763. doi: 10.1016/j.bpc.2022.106763. Epub 2022 Jan 22.

Authors

Anita Kotar¹, Sicong Ma², Sarah C Keane³

Affiliations

¹ Biophysics Program, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109, USA; Slovenian NMR Centre, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia.
² Biophysics Program, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109, USA.
³ Biophysics Program, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109, USA; Department of Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109, USA. Electronic address: sckeane@umich.edu.

Abstract

MicroRNAs (miRNAs) are important regulators of post-transcriptional gene expression. Mature miRNAs are generated from longer transcripts (primary, pri- and precursor, pre-miRNAs) through a series of highly coordinated enzymatic processing steps. The sequence and structure of these pri- and pre-miRNAs play important roles in controlling their processing. Both pri- and pre-miRNAs adopt hairpin structures with imperfect base pairing in the helical stem. Here, we investigated the role of three base pair mismatches (A∙A, G∙A, and C∙A) present in pre-miRNA-31. Using a combination of NMR spectroscopy and thermal denaturation, we found that nucleotides within the three base pair mismatches displayed unique structural properties, including varying dynamics and sensitivity to solution pH. These studies deepen our understanding of how the physical and chemical properties of base pair mismatches influence RNA structural stability.

Keywords: Base pair mismatch; Helical stem; Solution NMR spectroscopy; microRNA.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Base Pairing
Hydrogen-Ion Concentration
MicroRNAs*
RNA Processing, Post-Transcriptional*

Substances

MicroRNAs

Grants and funding

R35 GM138279/GM/NIGMS NIH HHS/United States