Unfolding the folding dynamics of RNA isoforms in senescence and aging

National Institute On Aging

Investigators

Abstract

We have utilized single-cell long-read cDNA sequencing to identify that a ribosomal protein gene, "RPS24," exhibits different RNA isoform expression patterns during proliferation and cellular senescence in human fibroblasts. Additionally, we have gathered bioinformatics data, including both DNA and RNA methylation, as well as bulk long-read cDNA sequencing data, to explore the interplay between gene expression and epigenetic regulation across different cellular states. Furthermore, we have employed nanopore dimethyl sulfate mutational profiling to determine isoform-specific structural profiles of RPS24 RNA transcripts in both proliferating and senescent conditions, and have conducted a preliminary analysis of their folding dynamics. By integrating single-cell sequencing, epigenetic profiling, and advanced RNA structural analysis, our research aims to uncover the complex regulatory mechanisms that govern RNA isoform expression and function in aging and cellular senescence.