N6-methyladenosine modifications of mRNAs and long noncoding RNAs in oxygen-induced retinopathy in mice

Yingqian Peng; Zicong Wang; Bingyan Li; Wei Tan; Jingling Zou; Yun Li; Shigeo Yoshida; Yedi Zhou

doi:10.1016/j.exer.2022.109114

N⁶-methyladenosine modifications of mRNAs and long noncoding RNAs in oxygen-induced retinopathy in mice

Exp Eye Res. 2022 Jul:220:109114. doi: 10.1016/j.exer.2022.109114. Epub 2022 May 15.

Authors

Yingqian Peng¹, Zicong Wang¹, Bingyan Li¹, Wei Tan¹, Jingling Zou¹, Yun Li¹, Shigeo Yoshida², Yedi Zhou³

Affiliations

¹ Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, 410011, China.
² Department of Ophthalmology, Kurume University School of Medicine, Kurume, Fukuoka, 830-0011, Japan.
³ Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, 410011, China. Electronic address: zhouyedi@csu.edu.cn.

PMID: 35584758
DOI: 10.1016/j.exer.2022.109114

Abstract

Retinal neovascular diseases are major causes of blindness worldwide. As a common epitranscriptomic modification of eukaryotic RNAs, N⁶-methyladenosine (m⁶A) is associated with the pathogenesis of many diseases, including angiogenesis, through the regulation of RNA metabolism and functions. The aim of this study was to identify m⁶A modifications of mRNAs and long noncoding RNAs (lncRNAs) and determine their potential roles in retinal neovascularization. The transcriptome-wide m⁶A profiles of mRNAs and lncRNAs in the retinal tissues of mice with oxygen-induced retinopathy (OIR) and controls were identified by microarray analysis of immunoprecipitated methylated RNAs. The m⁶A methylation levels of mRNAs and lncRNAs identified in the microarray data were validated by MeRIP-qPCR. A total of 1321 mRNAs (151 hypermethylated and 1170 hypomethylated) and 192 lncRNAs (15 hypermethylated and 177 hypomethylated) were differentially methylated with the m⁶A modification in OIR and control mice. Gene ontology analysis showed that hypermethylated mRNAs were enriched in the regulation of multicellular organismal process, intracellular organelle, and protein binding, while hypomethylated mRNAs were enriched in cellular metabolic process, intracellular process, and binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that hypermethylated mRNAs were involved in dopaminergic synapses, glutamatergic synapse, and PI3K-Akt signaling pathway, while hypomethylated mRNAs were involved in autophagy, ubiquitin-mediated proteolysis, and spliceosome. Moreover, the altered levels of m⁶A methylation of ANGPT2, GNG12, ROBO4, and ENSMUST00000153785 were validated by MeRIP-qPCR. The results revealed an altered m⁶A epitranscriptome in OIR retinas. These methylated RNAs may act as novel modulators and targets in retinal neovascularization.

Keywords: RNA methylation; Retinal neovascular disease; lncRNA; m(6)A; mRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine / analogs & derivatives
Animals
Gene Expression Profiling / methods
Mice
Oxygen / toxicity
Phosphatidylinositol 3-Kinases / genetics
RNA, Long Noncoding* / genetics
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptors, Cell Surface / genetics
Retinal Neovascularization* / genetics

Substances

RNA, Long Noncoding
RNA, Messenger
Receptors, Cell Surface
Robo4 protein, mouse
N-methyladenosine
Adenosine
Oxygen