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The N6-methyladenosine RNA landscape in the aged mouse hippocampus.
Huang, He; Song, Renhua; Wong, Justin J-L; Anggono, Victor; Widagdo, Jocelyn.
Afiliação
  • Huang H; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
  • Song R; Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia.
  • Wong JJ; The University of Sydney, Faculty of Medicine and Health, Camperdown, New South Wales, Australia.
  • Anggono V; Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia.
  • Widagdo J; The University of Sydney, Faculty of Medicine and Health, Camperdown, New South Wales, Australia.
Aging Cell ; 22(1): e13755, 2023 01.
Article em En | MEDLINE | ID: mdl-36495001
ABSTRACT
The aged brain is associated with an inevitable decline in cognitive function and increased vulnerability to neurodegenerative disorders. Multiple molecular hallmarks have been associated with the aging nervous system through transcriptomics and proteomic studies. Recently, epitranscriptomic analysis has highlighted the role of RNA chemical modification in various biological processes. In particular, N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic mRNAs, has been functionally linked to multiple aspects of RNA metabolism with the roles of m6A in processes such as learning and memory, leading to our current investigation of how the m6A-transcriptomic landscape is shaped during aging. Using the inbred C57BL/6 line, we compared the m6A-transcriptomic profiles from the hippocampi of young (3-month-old) and aged (20-month-old) mice. Methylated RNA immunoprecipitation (MeRIP)-sequencing analysis revealed hyper- and hypomethylation in 426 and 102 genes, respectively, in the aged hippocampus (fold change >1.5, false discovery rate <0.05). By correlating the methylation changes to their steady-state transcript levels in the RNA-Seq data, we found a significant concordance between m6A and transcript levels in both directions. Notably, the myelin regulator gene Gpr17 was downregulated in the aged hippocampus concomitant with reduced m6A levels in its 3'UTR. Using reporter constructs and mutagenesis analysis, we demonstrated that the putative m6A sites in the 3'UTR of Gpr17 are important for mRNA translation but not for regulating transcript stability. Overall, the positive correlation between m6A and the transcript expression levels indicates a co-transcriptional regulation of m6A with gene expression changes that occur in the aged mouse hippocampus.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA / Proteômica Limite: Animals Idioma: En Revista: Aging Cell Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA / Proteômica Limite: Animals Idioma: En Revista: Aging Cell Ano de publicação: 2023 Tipo de documento: Article