Non-coding RNA
Functional RNA molecules not translated into protein.
Non-coding RNA (ncRNA) is a functional RNA molecule that does not get translated into a protein. The DNA that serves as the template for a functional ncRNA is typically referred to as a non-coding gene or an RNA gene. Common and crucial types include transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), along with smaller varieties like microRNAs, siRNAs, piRNAs, snoRNAs, snRNAs, exRNAs, and scaRNAs, as well as longer ones such as Xist, HOTAIR, and MALAT1. How many non-coding RNAs exist in the human genome is not known, though transcriptomic and bioinformatic work suggests there are thousands of them. Many of these newly found ncRNAs have no known function, if they have any at all. There is disagreement over how much non-coding transcription actually serves a purpose: some researchers think most of it is non-functional "junk RNA" or accidental transcription, while others believe many of these transcripts have roles yet to be uncovered.
Nucleic acids were first identified in 1868 by Friedrich Miescher, and by 1939 RNA was known to be involved in protein synthesis. Two decades later, Francis Crick predicted that a functional RNA component mediated translation, reasoning that RNA could base-pair with an mRNA transcript more effectively than a pure polypeptide could. The first non-coding RNA to be characterized was an alanine tRNA from baker's yeast, with its structure published in 1965. To obtain a purified sample, Robert W. Holley and his team used 140 kilograms of commercial baker's yeast to produce just 1 gram of purified tRNAAla for analysis. This 80-nucleotide tRNA was sequenced by digesting it first with pancreatic ribonuclease (which produced fragments ending in cytosine or uridine) and then with takadiastase ribonuclease T1 (which gave fragments ending in guanosine). Chromatography and identification of the 5' and 3' ends helped arrange these fragments to determine the sequence. Of the three structures initially proposed for this tRNA, the "cloverleaf" shape was independently suggested in several later publications. That cloverleaf secondary structure was confirmed after X-ray crystallography by two separate research groups in 1974. Ribosomal RNA was discovered next, followed by snRNA (small nuclear RNA) in the 1960s and 1970s. Since then, new non-coding RNAs have continued to be found, including snoRNAs, Xist, CRISPR, and many others. Recent notable addit
- first_discovered
- 1868 (nucleic acids by Friedrich Miescher)
- first_ncRNA_characterized
- 1965 (alanine tRNA from baker's yeast)
- key_roles
- Translation, RNA splicing, DNA replication, gene regulation
- types_include
- tRNA, rRNA, microRNA, siRNA, piRNA, snoRNA, snRNA, Xist, HOTAIR, MALAT1
- functional_debate
- Some consider most ncRNAs junk RNA; others expect undiscovered functions
Lore & Background
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 mediating translation. The first non-coding RNA to be characterized was an alanine tRNA found in baker's yeast, its structure published in 1965. Robert W. Holley and colleagues used 140 kg of commercial baker's yeast to produce 1 g of purified tRNAAla for analysis. The 80-nucleotide tRNA was sequenced using digestion with pancreatic ribonuclease and takadiastase ribonuclease T1, followed by chromatography. Of three proposed structures, the 'cloverleaf' was independently suggested in several later publications and confirmed by X-ray crystallography in 1974. Ribosomal RNA was discovered next, followed by snRNA (small nuclear RNA) in the 1960s and 1970s. The 2006 Nobel Prize in Physiology or Medicine was awarded to Andrew Fire and Craig C. Mello for their discovery of RNA interference (RNAi)—a gene-silencing mechanism triggered by double-stranded RNA—which paved the way for understanding related pathways involving small RNAs like miRNA and siRNA.
Reader's Guide
Non-coding RNAs belong to several groups and are involved in many cellular processes, from those conserved across all cellular life to transient ncRNAs specific to a few species. Conserved ncRNAs are thought to be molecular fossils from the RNA world, mostly regulating information flow from DNA to protein. In translation, ribosomes consist of more than 60% rRNA, with 3 ncRNAs in prokaryotes and 4 in eukaryotes. Transfer RNAs act as adaptor molecules. snoRNAs guide covalent modifications of rRNA, tRNA, and snRNAs; RNase P matures tRNA sequences. In RNA splicing, the spliceosome contains ncRNA components such as U1, U2, U4, U5, and U6 in the major form, and U11, U12, U5, U4atac, and U6atac in the minor form. Self-splicing RNAs (group I and group II catalytic introns) catalyze their own excision. In gene regulation, microRNAs down-regulate expression via partial complementarity to mRNA. Other ncRNAs like 7SK RNA, 6S RNA, OxyS RNA, and B2 RNA regulate transcription or translation. The article notes that the number of ncRNAs in the human genome is unknown and that there is no consensus on how much non-coding transcription is functional.
Did You Know?
- The first non-coding RNA characterized was an alanine tRNA from baker's yeast, sequenced in 1965.
- Ribosomes consist of more than 60% ribosomal RNA, with 3 ncRNAs in prokaryotes and 4 in eukaryotes.
- The discovery of the RNAi mechanism associated with miRNA earned Craig C. Mello and Andrew Fire the 2006 Nobel Prize in Physiology or Medicine.
- There is no consensus on how much non-coding transcription is functional; some believe most ncRNAs are junk RNA.
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