The Yin and Yang of enhancer-like RNAs

Abstract

Long noncoding RNAs are emerging as a critical component of transcriptional activation. Over the past few years, there has been a number of examples where long noncoding RNAs expressed from distal sites exert their activating functions on neighbouring protein‐coding genes. A new study in The EMBO Journal (Lu et al , 2013) now extends this paradigm by revealing a role for the transcription factor Yin Yang 1 (YY1) in the regulation of the expression of long noncoding RNAs (termed Yams) during myogenesis. Importantly, the authors demonstrate a functional role for Yam‐1 in muscle differentiation through activation of a neighbouring micoRNA‐715 leading to downregulation of Wnt7b. There is converging evidence that distal regulatory sites commonly known as ‘enhancers’ are transcribed in a stimulus‐dependent manner as long noncoding RNAs (known as enhancer RNAs, eRNAs) and such eRNAs contribute to transcriptional activation of their neighbouring genes (De Santa et al , 2010; Kim et al , 2010; Hah et al , 2013; Lam et al , 2013; Li et al , 2013; Melo et al , 2013). Concomitantly, studies of long noncoding RNAs located in intergenic sites (termed lincRNAs, large intergenic noncoding RNAs) have uncovered a role for a class of lincRNAs (named noncoding RNA‐activating, ncRNA‐a) having enhancer‐like functions (Orom et al , 2010; Wang et al , 2011). These activating lincRNAs are enriched with transcription factor binding sites at their promoters and display responsiveness to differentiating stimuli (Orom et al, …