Small Molecule Alteration of RNA Sequence in Cells and Animals

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2017 Oct 29

PMID 29079470

Citations 3

Authors

Lirui Guan

Yiling Luo

William W Ja

Matthew D Disney

Affiliations

Soon will be listed here.

Abstract

RNA regulation and maintenance are critical for proper cell function. Small molecules that specifically alter RNA sequence would be exceptionally useful as probes of RNA structure and function or as potential therapeutics. Here, we demonstrate a photochemical approach for altering the trinucleotide expanded repeat causative of myotonic muscular dystrophy type 1 (DM1), r(CUG). The small molecule, 2H-4-Ru, binds to r(CUG) and converts guanosine residues to 8-oxo-7,8-dihydroguanosine upon photochemical irradiation. We demonstrate targeted modification upon irradiation in cell culture and in Drosophila larvae provided a diet containing 2H-4-Ru. Our results highlight a general chemical biology approach for altering RNA sequence in vivo by using small molecules and photochemistry. Furthermore, these studies show that addition of 8-oxo-G lesions into RNA 3' untranslated regions does not affect its steady state levels.

Citing Articles

Heterobifunctional small molecules to modulate RNA function.

Kovachka S, Tong Y, Childs-Disney J, Disney M Trends Pharmacol Sci. 2024; 45(5):449-463.

PMID: 38641489 PMC: 11774243. DOI: 10.1016/j.tips.2024.03.006.

Targeting RNA with Small Molecules To Capture Opportunities at the Intersection of Chemistry, Biology, and Medicine.

Disney M J Am Chem Soc. 2019; 141(17):6776-6790.

PMID: 30896935 PMC: 6541398. DOI: 10.1021/jacs.8b13419.

Molecular Therapies for Muscular Dystrophies.

Lin A, Wang L Curr Treat Options Neurol. 2018; 20(7):27.

PMID: 29926204 DOI: 10.1007/s11940-018-0509-2.

Targeting RNA in mammalian systems with small molecules.

Donlic A, Hargrove A Wiley Interdiscip Rev RNA. 2018; 9(4):e1477.

PMID: 29726113 PMC: 6002909. DOI: 10.1002/wrna.1477.

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