Noncoding RNAs (ncRNAs) are hardly a new discovery: from tRNA characterized in the 1960s to rRNA in the '80s and microRNA in the '90s, biologists have appreciated the important and versatile roles of RNAs that do not encode a protein. The advent of RNA sequencing and derivatives thereof—such as CaptureSeq—have yielded a number of new ncRNA classes, from large (sometimes intergenic) l(i)ncRNAs (defined as longer than 200 nucleotides without an open reading frame) to shorter transcripts derived from regulatory regions such as promoters and enhancers. Some short RNAs, including circular (cRNAs) and competing endogenous RNAs (ceRNAs), act as regulators of other ncRNAs such as microRNAs, but the function of the vast majority of these newly discovered ncRNAs has yet to be determined.

The many roles of ncRNA. Credit: Marina Corral Spence/Nature Publishing Group

Recent efforts to elucidate the role of some lncRNAs include laborious knockout experiments (eLife 2, e01749, 2013). More indirectly but on a larger scale, the study of expression levels, the propensity to degrade targets and the directionality of transcription has yielded insight into whether ncRNAs are signal or noise (Nat. Commun. 5, 5336, 2014), but a comprehensive characterization is still outstanding.

Structure and post-translational modifications in addition to binding partners need to be cataloged to understand mechanisms of ncRNA action. Particularly for lncRNAs, a unified nomenclature would help to better place new additions in the rapidly growing list and to define functional relationships. Improved computational tools to predict ncRNA sequences, and databases to compare newly discovered and existing structures, functions and impact on disease, will be invaluable.