한빛사 논문
Heeyoung Seok1, Haejeong Lee1,2, Sohyun Lee1, Seung Hyun Ahn1, Hye-Sook Lee1, Geun-Woo D. Kim1,2, Jongjin Peak1, Jongyeun Park1, You Kyung Cho1, Yeojin Jeong2, Dowoon Gu1, Yeahji Jeong1, Sangkyeong Eom1, Eun-Sook Jang1 & Sung Wook Chi1,2,*
1Department of Life Sciences, Korea University, Seoul, Korea. 2Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
*Correspondence to Sung Wook Chi.
Abstract
In pathophysiology, reactive oxygen species oxidize biomolecules that contribute to disease phenotypes1. One such modification, 8-oxoguanine2 (o8G), is abundant in RNA3 but its epitranscriptional role has not been investigated for microRNAs (miRNAs). Here we specifically sequence oxidized miRNAs in a rat model of the redox-associated condition cardiac hypertrophy4. We find that position-specific o8G modifications are generated in seed regions (positions 2–8) of selective miRNAs, and function to regulate other mRNAs through o8G•A base pairing. o8G is induced predominantly at position 7 of miR-1 (7o8G-miR-1) by treatment with an adrenergic agonist. Introducing 7o8G-miR-1 or 7U-miR-1 (in which G at position 7 is substituted with U) alone is sufficient to cause cardiac hypertrophy in mice, and the mRNA targets of o8G-miR-1 function in affected phenotypes; the specific inhibition of 7o8G-miR-1 in mouse cardiomyocytes was found to attenuate cardiac hypertrophy. o8G-miR-1 is also implicated in patients with cardiomyopathy. Our findings show that the position-specific oxidation of miRNAs could serve as an epitranscriptional mechanism to coordinate pathophysiological redox-mediated gene expression.
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