Enhancers Silence Coupled-coding RNAs in Animals

The exact working mechanism and biogenesis of regulatory non-coding RNAs (rncRNAs), including enhancer RNAs (eRNAs), microRNAs (miRNAs), piRNAs, small interfering RNAs (siRNAs), transposons, and other non-coding RNAs, remain enigmatic. Conversely, the unique transcriptional regulation mechanism that differentiates animals from simple unicellular organisms remains elusive in life sciences. We find that regulatory non-coding genes are independent transcription units marked with arginine methylation of nucleosomes within their gene bodies, which is regulated by JMJD5. Enhancer RNAs are similar to those of other regulatory RNAs in targeting the 3-prime UTRs of coupled coding RNAs. All regulatory RNA genes share transcription factors with their target coding genes, both of which are regulated by promoter-proximal RNA Polymerase II pausing and may control the development of animals. Temporal and spatial coding genes and regulatory non-coding genes are intrinsically coupled in animals.