Comprehensive Transcriptomic Profiling of m6A Modification in Age-Related Hearing Loss

Biomolecules. 2023 Oct 18;13(10):1537. doi: 10.3390/biom13101537.

Abstract

Age-related hearing loss (ARHL), also known as presbycusis, is one of the most common neurodegenerative disorders in elderly individuals and has a prevalence of approximately 70-80% among individuals aged 65 and older. As ARHL is an intricate and multifactorial disease, the exact pathogenesis of ARHL is not fully understood. There is evidence that transcriptional dysregulation mediated by epigenetic modifications is widespread in ARHL. However, the potential role of N6-methyladenosine (m6A) modification, as a crucial component of epigenetics, in ARHL progression remains unclear. In this study, we confirmed that the downregulation of m6A modification in cochlear tissues is related to ARHL and found that the expression of the m6A methylation regulators Wilms tumour suppressor-1-associated protein (WTAP), methyltransferase-like 3 (METTL3), ALKB homologous protein 5 (ALKBH5) and fat mass and obesity-associated protein (FTO) is decreased significantly at the mRNA and protein levels in ARHL mice. Then, we used methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and RNA sequencing (RNA-Seq) to identify the differentially m6A-methylated genes in the cochlear tissues of ARHL mice. A total of 3438 genes with differential m6A methylation were identified, of which 1332 genes were m6A-hypermethylated and 2106 genes were m6A-hypomethylated in the ARHL group compared to the control group according to MeRIP-seq. Further joint analysis of RNA-Seq and MeRIP-Seq data showed that 262 genes had significant differences in both mRNA expression and m6A methylation. GO and KEGG analyses indicated that 262 unique genes were enriched mainly in the PI3K-AKT signalling pathway. In conclusion, the results of this study reveal differential m6A methylation patterns in the cochlear tissues of ARHL mice, providing a theoretical basis for further study of the pathogenesis of ARHL and potential therapeutic strategies.

Keywords: MeRIP-Seq; RNA-Seq; age-related hearing loss; m6A modification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Animals
  • Gene Expression Profiling
  • Humans
  • Methyltransferases / genetics
  • Mice
  • Phosphatidylinositol 3-Kinases*
  • Presbycusis* / genetics
  • RNA, Messenger / genetics
  • Transcriptome / genetics

Substances

  • Phosphatidylinositol 3-Kinases
  • RNA, Messenger
  • METTL3 protein, human
  • Methyltransferases
  • FTO protein, human
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO

Grants and funding

This paper was funded by Major Programs of Chongqing Science and Health Union (No2022DBXM006). National Natural Science Foundation of China (No. 81873702) and Natural Science Foundation of Chongqing (No.2022NSCQ-MSX2839, Nos. CSTB2022NSCQ-MSX0553, 2023jsqd180). Young and Middle-aged Medical Excellence Team of Chongqing. Postdoctoral Science Foundation Project of Chongqing Natural Science Foundation (No. cstc2021jcyj-bshx0026).