Over the last decade, long noncoding RNAs (lncRNAs) have emerged as a 
fundamental molecular class whose members play pivotal roles in the regulation 
of the genome. The observation of pervasive transcription of mammalian genomes 
in the early 2000s sparked a revolution in the understanding of information flow 
in eukaryotic cells and the incredible flexibility and dynamic nature of the 
transcriptome. As a molecular class, distinct loci yielding lncRNAs are set to 
outnumber those yielding mRNAs. However, like many important discoveries, the 
road leading to uncovering this diverse class of molecules that act through a 
remarkable repertoire of mechanisms, was not a straight one. The same 
characteristic that most distinguishes lncRNAs from mRNAs, i.e. their 
developmental-stage, tissue-, and cell-specific expression, was one of the major 
impediments to their discovery and recognition as potentially functional 
regulatory molecules. With growing numbers of lncRNAs being assigned to 
biological functions, the specificity of lncRNA expression is now increasingly 
recognized as a characteristic that imbues lncRNAs with great potential as 
biomarkers and for the development of highly targeted therapeutics. Here we 
review the history of lncRNA research and how technological advances and insight 
into biological complexity have gone hand-in-hand in shaping this revolution. We 
anticipate that as increasing numbers of these molecules, often described as the 
dark matter of the genome, are characterized and the structure-function 
relationship of lncRNAs becomes better understood, it may ultimately be feasible 
to decipher what these non-(protein)-coding genes encode. This article is part 
of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by 
Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa.