Position-specific oxidation of miR-1 encodes cardiac hypertrophy

Heeyoung Seok, Haejeong Lee, Sohyun Lee, Seung Hyun Ahn, Hye-Sook Lee, Geun-Woo D. Kim, Jongjin Peak, Jongyeun Park, You Kyung Cho, Yeojin Jeong, Dowoon Gu, Yeahji Jeong, Sangkyeong Eom, Eun-Sook Jang and Sung Wook Chi ()
Additional contact information
Heeyoung Seok: Korea University
Haejeong Lee: Korea University
Sohyun Lee: Korea University
Seung Hyun Ahn: Korea University
Hye-Sook Lee: Korea University
Geun-Woo D. Kim: Korea University
Jongjin Peak: Korea University
Jongyeun Park: Korea University
You Kyung Cho: Korea University
Yeojin Jeong: Korea University
Dowoon Gu: Korea University
Yeahji Jeong: Korea University
Sangkyeong Eom: Korea University
Eun-Sook Jang: Korea University
Sung Wook Chi: Korea University

Nature, 2020, vol. 584, issue 7820, 279-285

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-020-2586-0 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:584:y:2020:i:7820:d:10.1038_s41586-020-2586-0

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-2586-0

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().