Non-coding RNAs in human disease

The non-protein-coding genome is gaining prominence in biology and medicine. The most well-studied non-coding RNAs (ncRNAs) are microRNAs (miRNAs), but many other types of ncRNAs also have major roles in cellular homeostasis and disease.These additional ncRNAs include PIWI-interacting RNAs (piRNAs), ncRNAs that are associated with transcription start sites, small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs), such as large intergenic non-coding RNAs (lincRNAs) and transcribed ultraconserved regions (T-UCRs). The list is not exclusive, and in many instances there is no clear molecular distinction between the classes, in part because many ncRNAs have unknown functions. However, there are some well-studied lncRNAs, such as homeobox (HOX) transcript antisense RNA (HOTAIR) and X-inactivation specific transcript (XIST), which are involved in transcriptional regulation.The recognition of the role of ncRNAs in disease has been derived from the existence of aberrant miRNA expression profiles in human cancer, where these transcripts, and their processing machineries, undergo genetic and epigenetic disruption. Other ncRNAs, such as T-UCRs and lncRNAs, are show aberrant expression levels in transformed cells.Cancer showed the way, but ncRNAs are involved in most human diseases, from neurological disorders to cardiovascular problems. Specific miRNAs are disrupted in intellectual disabilities and neurodegerative syndromes and contribute to atherosclerosis, and snoRNA and lncRNA functions are impaired in imprinting syndromes.These alterations of ncRNA expression and/or function in disease suggest that therapies targeting these molecules might be useful. Most of these approaches usually involve antisense oligonucleotides directed against miRNAs, but small molecule drugs that act on the miRNA machinery are also an interesting alternative pathway to explore, and similar strategies can also target other ncRNAs.A key challenge comes from the little basic knowledge that exists about the normal function of some ncRNAs, particularly lncRNAs. The alliance between 'wet' laboratory scientists (that is, molecular and cellular biomedical researchers) and 'dry' laboratory scientists (that is, bioinformaticians) promises to be decisive in solving this exciting puzzle.