Evidence for important, including essential, cellular and organismal roles of lncRNA in mammalian systems began to emerge prior to the advent of high-throughput genome and transcriptome sequencing. These early examples included the demonstration that the lncRNA XIST [1] was necessary and sufficient for X-chromosome silencing, as well as the discovery of SRA [2], an lncRNA that directly regulates the estrogen receptor α, one of the nuclear hormone receptors. Other essential functional ncRNAs in eukaryotic cells, such as ribosomal, transfer, and spliceosomal RNAs, have been well-known for an even longer time. Although the human genome project [3] initially focused almost exclusively on protein-coding genes in the human gene count, the ubiquity, in addition to the existence and the functional significance, of mammalian lncRNAs has been a key revelation of transcriptome sequencing projects [4].
