Comprehensive Analysis of Long Non-Coding RNAs N4-Acetylcytidine in Alzheimer’s Disease Mice Model Using High-Throughput Sequencing

Article type: Research Article

Authors: Ma, Yanzhen^a | Li, Weizu^d | Fan, Chang^a | Wang, Yongzhong^{b; e} | Jiang, Hui^{a; b; *} | Yang, Wenming^{b; c; *}

Affiliations: [a] Experimental Center of Clinical Research, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China | [b] Key Laboratory of Xin’an Medicine of the Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, China | [c] Encephalopathy Center, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China | [d] Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, Anhui, China | [e] Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China

Correspondence: [*] Correspondence to: Hui Jiang and Wenming Yang, Key Laboratory of Xin’an Medicine of the Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, China, E-mails: [email protected] and [email protected].

Abstract: Background:N4-acetylcytidine (ac4C), an important posttranscriptional modification, is involved in various disease processes. Long noncoding RNAs (lncRNAs) regulate gene expression mainly through epigenetic modification, transcription, and posttranscriptional modification. Alzheimer’s disease (AD) is a neurodegenerative disease characterized by amyloidosis of the brain. However, the role of lncRNA ac4C modification in AD remains unclear. Objective:In this study, we investigated the association between ac4C modification and AD, and the underlying mechanisms of ac4C modification in AD. Methods:The male 9-month-old APP/PS1 double transgenic mice, age- and sex-matched wild type (WT) mice were used in this study. Then, ac4C-RIP-seq and RNA-seq were used to comprehensively analyze lncRNA ac4C modification in AD mice. The lncRNA-miRNA-mRNA regulatory networks using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed the regulatory relationships among these three lncRNAs and AD. Results:The results showed that there were 120 significantly different ac4C peaks located on 102 lncRNAs in AD, of which 55 were hyperacetylated and 47 were hypoacetylated. Simultaneously, 231 differentially expressed lncRNAs were identified, including 138 upregulated lncRNAs and 93 downregulated lncRNAs. Moreover, 3 lncRNAs, lncRNA Gm26508, lncRNA A430046D13Rik, and lncRNA 9530059O14Rik, showed significant changes in both the ac4C and RNA levels using conjoint analysis. Conclusion:The abundance of lncRNA ac4C modification is significantly different in AD and indicates that lncRNA ac4C is associated with the occurrence and development of AD, which could provide a basis for further exploration of the related regulatory mechanisms.

Keywords: ac4C acetylation, Alzheimer’s disease, high-throughput sequencing, lncRNAs

DOI: 10.3233/JAD-220564

Journal: Journal of Alzheimer's Disease, vol. 90, no. 4, pp. 1659-1675, 2022