A new role for miRNAs: Transcriptional Gene Activation by Nuclear Activating miRNA (namiRNAs)
MiRNAs are small non-coding RNAs that carry diverse epigenetic and post-transcriptional mechanisms. Primarily, they have been studied for their function as a negative gene expression regulator, leaving their roles in activating gene expression poorly understood. Xiao et al.reports that miRNAs in the nucleus mediate gene activation by interacting with enhancer elements through epigenetic alteration.
Through screening the microRNA database, Xiao et al. identified a subset of microRNAs that function as enhancer regulators and further activate global gene activation, which the group termed “namiRNAs” (nuclear activating miRNA). They focused on miR-24-1 and found that this microRNA unconventionally activates gene transcription by targeting enhancers. Consistently, this activation was completely abolished when the enhancer sequence was deleted by TALEN. They also found that miR-24-1 activates enhancer RNA (eRNA) expression, alters histone modification, and increases the enrichment of p300 and RNA Pol II at the enhancer locus. Therefore, their results demonstrate a novel mechanism of microRNA as an enhancer trigger.
These results have greatly advanced our knowledge of microRNAs function, which moves us towards a more holistic understanding of this unusual microRNA. However, how these namiRNAs mechanistically perform this unconventional function also remains largely unclear. Current research is unfortunately much too sporadic and narrow, with most individual reports focusing on merely one microRNA’s up-regulating function, or the reported miRNA is usually shown to only perform the up-regulating function under specific, restrictive conditions that does not apply to a broader context. Arguably then, although research has left many unanswered questions, we believe that this new uncanonical activation function of namiRNAs will be appreciated by a more extensive audience.
Xiao M, Li J, Li W, Wang Y, Wu F, Xi Y, Zhang L, Ding C, Luo H, Li Y, Peng L, Zhao L, Peng S, Xiao Y, Dong S, Cao J, & Yu W (2016). MicroRNAs Activate Gene Transcription Epigenetically as an Enhancer Trigger. RNA biology PMID: 26853707