Characterizing microRNA editing and mutation sites in Autism Spectrum Disorder

Xingwang Wu; Huaide Yang; Han Lin; Angbaji Suo; Shuai Wu; Wenping Xie; Nan Zhou; Shiyong Guo; Hao Ding; Guangchen Zhou; Zhichao Qiu; Hong Shi; Jun Yang; Yun Zheng

doi:10.3389/fnmol.2022.1105278

Characterizing microRNA editing and mutation sites in Autism Spectrum Disorder

Front Mol Neurosci. 2023 Jan 20:15:1105278. doi: 10.3389/fnmol.2022.1105278. eCollection 2022.

Authors

Xingwang Wu^{1

2}, Huaide Yang³, Han Lin⁴, Angbaji Suo^{1

2}, Shuai Wu^{1

2}, Wenping Xie^{1

2}, Nan Zhou³, Shiyong Guo^{1

2}, Hao Ding³, Guangchen Zhou³, Zhichao Qiu^{1

2}, Hong Shi^{1

2}, Jun Yang⁵, Yun Zheng^{1

2

3

6}

Affiliations

¹ State Key Laboratory of Primate Biomedical Research, Kunming University of Science and Technology, Kunming, Yunnan, China.
² Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China.
³ Faculty of Information Engineering and Automation, Kunming University of Science and Technology, Kunming, Yunnan, China.
⁴ Department of Urology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
⁵ School of Criminal Investigation, Yunnan Police College, Kunming, Yunnan, China.
⁶ College of Landscape and Horticulture, Yunnan Agricultural University, Kunming, Yunnan, China.

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder whose pathogenesis is still unclear. MicroRNAs (miRNAs) are a kind of endogenous small non-coding RNAs that play important roles in the post-transcriptional regulation of genes. Recent researches show that miRNAs are edited in multiple ways especially in central nervous systems. A-to-I editing of RNA catalyzed by Adenosine deaminases acting on RNA (ADARs) happens intensively in brain and is also noticed in other organs and tissues. Although miRNAs are widely edited in human brain, miRNA editing in ASD is still largely unexplored. In order to reveal the editing events of miRNAs in ASD, we analyzed 131 miRNA-seq samples from 8 different brain regions of ASD patients and normal controls. We identified 834 editing sites with significant editing levels, of which 70 sites showed significantly different editing levels in the superior frontal gyrus samples of ASD patients (ASD-SFG) when compared with those of control samples. The editing level of an A-to-I editing site in hsa-mir-376a-1 (hsa-mir-376a-1_9_A_g) in ASD-SFG is higher than that of normal controls, and the difference is exaggerated in individuals under 10 years. The increased expression of ADAR1 is consistent with the increased editing level of hsa-mir-376a-1_9_A_g in ASD-SFG samples compared to normal SFG samples. Furthermore, we verify that A-to-I edited hsa-mir-376a-5p directly represses GPR85 and NAPB, which may contribute to the abnormal neuronal development of ASD patients. These results provide new insights into the mechanism of ASD.

Keywords: Autism Spectrum Disorder; GPR85; NAPB; hsa-miR-376a-5p; miRNA editing.

Grants and funding

The research was supported in part by a grant (No. 31460295) of the National Natural Science Foundation of China (http://www.nsfc.gov.cn/), an open research fund (No. SKLGE-2107) of the State Key Laboratory of Genetic Engineering, Fudan University, China, to YZ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.