Non-coding RNA

A non-coding RNA (ncRNA) is an RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non-coding RNAs include transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), as well as small RNAs such as microRNAs, siRNAs, piRNAs, snoRNAs, snRNAs, exRNAs, scaRNAs and the long ncRNAs such as Xist and HOTAIR. A non-coding RNA (ncRNA) is an RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non-coding RNAs include transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), as well as small RNAs such as microRNAs, siRNAs, piRNAs, snoRNAs, snRNAs, exRNAs, scaRNAs and the long ncRNAs such as Xist and HOTAIR. The number of non-coding RNAs within the human genome is unknown; however, recent transcriptomic and bioinformatic studies suggest that there are thousands of them. Many of the newly identified ncRNAs have not been validated for their function. It is also likely that many ncRNAs are non functional (sometimes referred to as junk RNA), and are the product of spurious transcription. Non-coding RNAs contribute to diseases including cancer and Alzheimer's. Nucleic acids were first discovered in 1868 by Friedrich Miescher and by 1939 RNA had been implicated in protein synthesis. Two decades later, Francis Crick predicted a functional RNA component which mediated translation; he reasoned that RNA is better suited to base-pair with an mRNA transcript than a pure polypeptide. The first non-coding RNA to be characterised was an alanine tRNA found in baker's yeast, its structure was published in 1965. To produce a purified alanine tRNA sample, Robert W. Holley et al. used 140kg of commercial baker's yeast to give just 1g of purified tRNAAla for analysis. The 80 nucleotide tRNA was sequenced by first being digested with Pancreatic ribonuclease (producing fragments ending in Cytosine or Uridine) and then with takadiastase ribonuclease Tl (producing fragments which finished with Guanosine). Chromatography and identification of the 5' and 3' ends then helped arrange the fragments to establish the RNA sequence. Of the three structures originally proposed for this tRNA, the 'cloverleaf' structure was independently proposed in several following publications. The cloverleaf secondary structure was finalised following X-ray crystallography analysis performed by two independent research groups in 1974. Ribosomal RNA was next to be discovered, followed by URNA in the early 1980s. Since then, the discovery of new non-coding RNAs has continued with snoRNAs, Xist, CRISPR and many more. Recent notable additions include riboswitches and miRNA; the discovery of the RNAi mechanism associated with the latter earned Craig C. Mello and Andrew Fire the 2006 Nobel Prize in Physiology or Medicine. Recent discoveries of ncRNAs have been achieved through both experimental and bioinformatic methods. Noncoding RNAs belong to several groups and are involved in many cellular processes. These range from ncRNAs of central importance that are conserved across all or most cellular life through to more transient ncRNAs specific to one or a few closely related species. The more conserved ncRNAs are thought to be molecular fossils or relics from the last universal common ancestor and the RNA world, and their current roles remain mostly in regulation of information flow from DNA to protein. Many of the conserved, essential and abundant ncRNAs are involved in translation. Ribonucleoprotein (RNP) particles called ribosomes are the 'factories' where translation takes place in the cell. The ribosome consists of more than 60% ribosomal RNA; these are made up of 3 ncRNAs in prokaryotes and 4 ncRNAs in eukaryotes. Ribosomal RNAs catalyse the translation of nucleotide sequences to protein. Another set of ncRNAs, Transfer RNAs, form an 'adaptor molecule' between mRNA and protein. The H/ACA box and C/D box snoRNAs are ncRNAs found in archaea and eukaryotes. RNase MRP is restricted to eukaryotes. Both groups of ncRNA are involved in the maturation of rRNA. The snoRNAs guide covalent modifications of rRNA, tRNA and snRNAs; RNase MRP cleaves the internal transcribed spacer 1 between 18S and 5.8S rRNAs. The ubiquitous ncRNA, RNase P, is an evolutionary relative of RNase MRP. RNase P matures tRNA sequences by generating mature 5'-ends of tRNAs through cleaving the 5'-leader elements of precursor-tRNAs. Another ubiquitous RNP called SRP recognizes and transports specific nascent proteins to the endoplasmic reticulum in eukaryotes and the plasma membrane in prokaryotes. In bacteria Transfer-messenger RNA (tmRNA) is an RNP involved in rescuing stalled ribosomes, tagging incomplete polypeptides and promoting the degradation of aberrant mRNA.