Project description:Aged brain is associated with an inevitable decline in cognitive functions and increased vulnerability to neurodegenerative disorders. Multiple molecular hallmarks have been associated with the aging nervous system through transcriptomics and proteomic studies. Recently, the field of epitranscriptomics highlights 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 processing. Importantly, the functional roles of m6A in neurophysiology, such as in the process of learning and memory, have led to our current investigation of how 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. The methylated RNA immunoprecipitation (MeRIP)-sequencing analysis revealed hyper- and hypo-methylation in 426 and 102 genes, respectively, in the aged hippocampus (fold-change >1.5, FDR<0.05). By correlating the methylation changes to their steady state transcript levels in the RNA-seq, we found a significant concordance between m6A and transcript levels in either direction.
Project description:Aged brain is associated with an inevitable decline in cognitive functions and increased vulnerability to neurodegenerative disorders. Multiple molecular hallmarks have been associated with the aging nervous system through transcriptomics and proteomic studies. Recently, the field of epitranscriptomics highlights 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 processing. Importantly, the functional roles of m6A in neurophysiology, such as in the process of learning and memory, have led to our current investigation of how 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. The methylated RNA immunoprecipitation (MeRIP)-sequencing analysis revealed hyper- and hypo-methylation in 426 and 102 genes, respectively, in the aged hippocampus (fold-change >1.5, FDR<0.05). By correlating the methylation changes to their steady state transcript levels in the RNA-seq, we found a significant concordance between m6A and transcript levels in either direction.
