Emerging insights into enhancer RNAs: biogenesis, function, mechanism, and disease implication.

Abstract

In current years, the molecular mechanisms through which enhancer-derived noncoding RNAs-enhancer RNAs (eRNAs) have been increasingly elucidated. eRNAs are not mere as transcript products but considered as a marker of active enhancers, usually characterized by bidirectional transcription, lack of poly(A) tails and rapid degradation. Multiple lines of evidence have demonstrated eRNAs are involved in a number of regulation processes such as enhancer-promoter (E-P) looping, recruitment of transcriptional co-activators, regulation of RNA polymerase II (Pol II) pause release, and induction of R-loops, thereby enabling precise control of gene expression. Besides, the tissue-specific regulatory mechanisms of eRNAs in diverse diseases such as cancer, cardiovascular diseases, and neurodegenerative disorders are being progressively elucidated, offering potential novel targets for precision diagnosis and therapy. This review systematically synthesizes recent advances in eRNA research, elucidating structural features, transcription processes, functions, regulatory mechanisms, detection, data resources, disease associations and proposing promising prospects for eRNA-targeted precision therapeutics.