Transcription regulation by RNA-induced structural strain in duplex DNA

Non-coding RNAs belong to a heterogenous family that, among other functions, acts as a biomolecular regulator of gene expression. In particular, lncRNAs, which are estimated to be as numerous as coding RNAs in humans, are thought to interact with genomic DNA to form triple helices. However, experimental evidence of their involvement with processes, such as chromatin structure dynamics or RNA transcription, is still missing. Here, a mechanism of transcription enhancement/inhibition is described, where hybrid RNA-DNA triplexes regulate transcription rates in Escherichia coli promoter-based designed architectures. Sequences associated with triplexes were identified in a library of bacterial promoters and characterized in vitro, followed by a synthetic biology approach to verify their ability to control transcription and translation. A model of the triplex-promoter complex was produced showing that transcription enhancement is due to a distortion of the duplex DNA as a consequence of its conjugation with RNA in the triplex assembly. These results point at a mechanism of RNA function that is still unknown and could be common in more complex organisms, such as metazoans including mammals, where non-coding RNAs are more abundant and are believed to play a fundamental role in determining hetero/euchromatin and transcription modulation.