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Functional impacts of non-coding RNA processing on enhancer activity and target gene expression
Evgenia Ntini 1,2,* and Annalisa Marsico 1,2,3,*
1 Max Planck Institute for Molecular Genetics, 14195, Berlin, Germany
2 Free University Berlin, 14195, Berlin, Germany
3 Institute of Computational Biology, Helmholtz Zentrum München, München, Germany
*Correspondence to:Evgenia Ntini, E-mail: ntini@molgen.mpg.de; Annalisa Marsico, E-mail: marsico@molgen.mpg.de
J Mol Cell Biol, Volume 11, Issue 10, October 2019, Pages 868-879  https://doi.org/10.1093/jmcb/mjz047
Keyword: transcription, enhancer, RNA processing, cotranscriptional RNA splicing, chromatin, long non-coding RNA (lncRNA)

Tight regulation of gene expression is orchestrated by enhancers. Through recent research advancements, it is becoming clear that enhancers are not solely distal regulatory elements harboring transcription factor binding sites and decorated with specific histone marks, but they rather display signatures of active transcription, showing distinct degrees of transcription unit organization. Thereby, a substantial fraction of enhancers give rise to different species of non-coding RNA transcripts with an unprecedented range of potential functions. In this review, we bring together data from recent studies indicating that non-coding RNA transcription from active enhancers, as well as enhancer-produced long non-coding RNA transcripts, may modulate or define the functional regulatory potential of the cognate enhancer. In addition, we summarize supporting evidence that RNA processing of the enhancer-associated long non-coding RNA transcripts may constitute an additional layer of regulation of enhancer activity, which contributes to the control and final outcome of enhancer-targeted gene expression.