Rewired m6A methylation of promoter antisense RNAs in Alzheimer's disease regulates global gene transcription in the 3D nucleome.

ABSTRACT: N ⁶ -methyladenosine (m6A) is the most prevalent internal RNA modification that can impact mRNA expression post-transcriptionally. Recent progress indicates that m6A also acts on nuclear or chromatin-associated RNAs to impact transcriptional and epigenetic processes. However, the landscapes and functional roles of m6A in human brains and neurodegenerative diseases, including Alzheimer's disease (AD), have been under-explored. Here, we examined RNA m6A methylome using total RNA-seq and meRIP-seq in middle frontal cortex tissues of post-mortem human brains from individuals with AD and age-matched counterparts. Our results revealed AD-associated alteration of m6A methylation on both mRNAs and various noncoding RNAs. Notably, a series of p romoter a ntisense RNAs (paRNAs) displayed

SUBMITTER: Hu B 

PROVIDER: S-EPMC11974732 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature