Direct roles of long non-coding RNAs in transcription activation

Gene expression begins with transcription initiation. However, the control of gene activation encompasses events that precede transcription and extend beyond it, and that are prominently regulated by the noncoding genome. Here we discuss the pivotal roles of long noncoding RNAs (lncRNAs) and the related enhancer RNAs (eRNAs) as genomic rheostats of the magnitude and duration of activation of transcription by RNA polymerase II, acting in trans by influencing general transcription factors and co-transcriptional and post-transcriptional processes, and in cis through their interactions with enhancers, promoters and other noncoding RNA genes. We further discuss how these lncRNAs are often produced at active enhancers or boundaries of topologically associating domains and can accumulate in biomolecular condensates. We propose models of lncRNA action that account for pre-existing chromatin states, and for the interactions between DNA, RNA and proteins. Understanding how lncRNAs fit within the dynamic process of transcription activation is essential for obtaining a comprehensive view of the regulation of gene expression.