1的位置特异性氧化编码心脏肥大

产品分类

新闻资讯

联系我们

凤凰资讯

当前位置:主页 > 凤凰资讯 >

1的位置特异性氧化编码心脏肥大

2020-08-06 20:26

本期文章:《自然》:Online/在线发表

韩国高丽大学Sung Wook Chi研究组发现,miR-1的位置特异性氧化编码心脏肥大。相关论文于2020年8月5日发表在《自然》杂志上。

他们在氧化还原相关疾病心肌肥大的大鼠模型中对氧化的microRNA(miRNA)进行了特异性测序。他们发现特定位置的8-氧代鸟嘌呤2(o8G)修饰是在选择性miRNA的种子区域(位置2-8)中产生的,并通过o8GA碱基配对来调节其他mRNA。通过用肾上腺素能激动剂治疗,主要在miR-1(7o8G-miR-1)的7位诱导了o8G。单独引入7o8G-miR-1或7U-miR-1(其中7位的G被U取代)足以引起小鼠心脏肥大,o8G-miR-1的mRNA靶标在受影响的表型中起作用,对小鼠心肌细胞7o8G-miR-1的特异性抑制可减轻心脏肥大。o8G-miR-1也与心肌病患者有关。

他们的发现表明,miRNA的位置特异性氧化可以作为表观转录机制来协调病理生理学氧化还原介导的基因表达。

据了解,在病理生理学中,活性氧会氧化导致疾病表型的生物分子。8-氧代鸟嘌呤2(o8G)修饰,在RNA3中含量很高,但尚未对其miRNA的表位转录作用进行研究。

附:英文原文

Title: Position-specific oxidation of miR-1 encodes cardiac hypertrophy

Author: 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, Sung Wook Chi

Issue&Volume: 2020-08-05

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 o8GA 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.

DOI: 10.1038/s41586-020-2586-0

Source: https://www.nature.com/articles/s41586-020-2586-0

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:
投稿链接:

地址:广东省广州市天河区88号 版权所有:Copyright © 2002-2019 美高梅网址 版权所有

技术支持:织梦58

扫一扫,加关注