Background: Cellular senescence is accompanied by extensive epigenomic reprogramming leading to changes in enhancer RNA levels, yet how enhancer activity is translated into functional RNA-level regulation remains unclear. Here we investigate how enhancer reprogramming during senescence impacts functional RNA-level regulation by eRNAs. Results: By integrating time-resolved transcriptomic analyses across multiple primary human cell types, we identify a set of recurrently dysregulated senescence-associated enhancer RNAs (SAeRs). We focus on one of these transcripts, EN526, which is reproducibly repressed during senescence while its locus remains broadly stable across cell states. EN526 eRNA exhibits cytoplasmic localisation and extensive eRNA-mRNA interactions, and cytoplasmic depletion of EN526 recapitulates its senescence-associated loss and alters the stability and translation of the cell-cycle regulator CDKN2C. EN526 perturbation further mediates stress responses, cellular survival, and extracellular remodelling associated with the senescence phenotype. Conclusion: Together, these findings show that SAeRs changes accompanying enhancer reprogramming in senescence are not merely passive events but can act as functional intermediates linking enhancer dynamics to post-transcriptional regulatory networks that phenocopy key senescence-associated cellular features. Extending this model, genetic associations at the EN526 locus further connect this regulatory axis to age-related traits and circulating protein phenotypes, supporting its broader relevance to human ageing and disease.
From Causal Discovery to Dynamic Causal Inference in Neural Time Series
arXiv:2603.20980v1 Announce Type: cross Abstract: Time-varying causal models provide a powerful framework for studying dynamic scientific systems, yet most existing approaches assume that the underlying