Small molecule alteration of RNA sequence in cells and animals

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:28

Article

Guan, Lirui¹  Luo, Yiling¹  Ja, William W.²  Disney, Matthew D.¹ 

[1] Scripps Res Inst, Dept Chem, Jupiter, FL 33458 USA

[2] Scripps Res Inst, Ctr Aging, Dept Neurosci, Jupiter, FL 33458 USA

关键词: RNA;    Small molecules;    Chemical probes;    Photochemistry;    Myotonic dystrophy;   

DOI  :  10.1016/j.bmcl.2017.10.034

来源: Elsevier

【 摘 要 】

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)(exp). The small molecule, 2H-4-Ru, binds to r(CUG)(exp) 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. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

Free