Enhancer RNAs: transcriptional regulators and workmates of NamiRNAs in myogenesis

Abstract

AbstractmiRNAs are well known to be gene repressors. A newly identified class of miRNAs termed nuclear activating miRNAs (NamiRNAs), transcribed from miRNA loci that exhibit enhancer features, promote gene expression via binding to the promoter and enhancer marker regions of the target genes. Meanwhile, activated enhancers produce endogenous non-coding RNAs (named enhancer RNAs, eRNAs) to activate gene expression. During chromatin looping, transcribed eRNAs interact with NamiRNAs through enhancer-promoter interaction to perform similar functions. Here, we review the functional differences and similarities between eRNAs and NamiRNAs in myogenesis and disease. We also propose models demonstrating their mutual mechanism and function. We conclude that eRNAs are active molecules, transcriptional regulators, and partners of NamiRNAs, rather than mere RNAs produced during enhancer activation.

Noncanonical functions of microRNAs in the nucleus

“…Subsequently, mature eRNAs bind to p300/CBP and other proteins to induce activation markers at the target gene promoters. Pol II and other transcription factors then attach to the gene promoter and activate target gene expression [ 69 , 70 ].…”

Nuclear miRNAs: gene regulation activities

“…Once transcribed, the eRNA interacts with the promoter of nearby located genes to promote their transcription (Figure 2(B2)). The gene locus of miR-26a-1 is located near to the genes coding for the ITGA9, CTDSPL, VILL and PLCD1 proteins [51,52]. It has been shown that when miR-26a-1 is overexpressed, there is a transcriptional activation of the ITGA9 and VILL genes.…”

Emerging roles of non-coding RNAs in colorectal cancer oxaliplatin resistance and liquid biopsy potential

“…Intriguingly, numerous recent studies have demonstrated that some miRNAs activate gene transcription unconventionally in the nucleus by targeting enhancers, such miRNAs are known as nuclear activating miRNAs[ 46 ]. Moreover, enhancers (including super-enhancers) have been revealed to synergistically promote NamiRNA biogenesis and activate the expression of proximal genes[ 47 , 48 ]. Furthermore, studies have reported that the dysregulation of miRNAs may play an important role in CRC oxaliplatin resistance, as illustrated in Table 1 .…”