@article{55e2fb38cc134ff585d2005ee50b082f,
title = "Position-specific oxidation of miR-1 encodes cardiac hypertrophy",
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.",
author = "Heeyoung Seok and Haejeong Lee and Sohyun Lee and Ahn, {Seung Hyun} and Lee, {Hye Sook} and Kim, {Geun Woo D.} and Jongjin Peak and Jongyeun Park and Cho, {You Kyung} and Yeojin Jeong and Dowoon Gu and Yeahji Jeong and Sangkyeong Eom and Jang, {Eun Sook} and Chi, {Sung Wook}",
note = "Funding Information: Acknowledgements We thank all members of the Chi laboratory for help and discussions. We thank in particular M.-H. Chung for sharing research experiences with H. Kasai and S. Nishimura, which inspired us to initiate this project; the late S.-D. Yoo for scientific discussions; the late Y.-S. Lee for initial help on this work; D.-Z. Wang for providing the pJG/ALPHA MHC vector; J. Han, H.-W. Lee and W. J. Park for providing AC16 cells and Y. W. Chung for H9c2 cells, which were used for preliminary studies; Samsung Medical Center for echocardiograms; J. Im and J. W. Park for initial help with the HPLC analysis to confirm the o8G immunoprecipitation; E. S. Cho for help in analysing sequence conservation of miR-1 oxo sites; D. H. Lee and W. Lee for initial help with the project; and the staff of Gyerim Experimental Animal Resource Center for animal care and technical assistance. This work was supported by Samsung Research Funding and Incubation Center of Samsung Electronics under project number SRFC-MA1801-10 and Korea University Grant. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2020",
month = aug,
day = "13",
doi = "10.1038/s41586-020-2586-0",
language = "English",
volume = "584",
pages = "279--285",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7820",
}