Non-coding RNA
Functional RNA molecules not translated into protein.
Non-coding RNA (ncRNA) refers to an RNA molecule that performs a function without ever being translated into a protein. The stretch of DNA that gives rise to such an RNA is typically called a non-coding gene or an RNA gene. Among the most common and crucial types are transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), along with smaller varieties like microRNAs, siRNAs, piRNAs, snoRNAs, snRNAs, exRNAs, and scaRNAs, plus long ncRNAs such as Xist, HOTAIR, and MALAT1. Exactly how many non-coding RNAs exist in the human genome remains unknown, though transcriptomic and bioinformatic work suggests there are thousands of these transcripts. Many newly identified ncRNAs have no known function, if they have one at all. Scientists disagree on how much of this non-coding transcription is actually useful: some consider most of it to be non-functional "junk RNA" or spurious transcription, while others believe many of these transcripts will eventually be found to have roles.
Nucleic acids were first isolated in 1868 by Friedrich Miescher, and by 1939 RNA was already linked to 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 easily than a pure polypeptide could. The first non-coding RNA to be characterized was an alanine tRNA from baker’s yeast, whose structure was published in 1965. To obtain a purified sample, Robert W. Holley and his team used 140 kilograms of commercial baker’s yeast to yield just 1 gram of pure tRNAAla for analysis. This 80-nucleotide tRNA was sequenced by digesting it 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 piece the fragments together to determine the sequence. Of the three structures originally proposed for this tRNA, the "cloverleaf" model was independently suggested in several later publications. The cloverleaf secondary structure was confirmed after X-ray crystallography by two separate research groups in 1974. Ribosomal RNA was discovered next, followed by URNA in the early 1980s. Since then, new non-coding RNAs have continued to appear, including snoRNAs, Xist, CRISPR, and many others. Recent notable finds include riboswitc
- first discovered
- 1868 (nucleic acids by Friedrich Miescher)
- first ncRNA characterized
- 1965 (alanine tRNA in baker's yeast)
- key types
- tRNA, rRNA, microRNA, siRNA, piRNA, snoRNA, snRNA, Xist, HOTAIR, MALAT1
- known for
- Regulation of translation, splicing, DNA replication, and gene expression
- discovery method
- Experimental and bioinformatic methods
- Nobel Prize associated
- 2006 (Craig C. Mello and Andrew Fire for RNAi mechanism)
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 et al. used 140 kg of commercial baker's yeast to give just 1 g of purified tRNAAla for analysis. The 80 nucleotide tRNA was sequenced by digestion with pancreatic ribonuclease and takadiastase ribonuclease T1, followed by chromatography. Of the three structures originally proposed, the 'cloverleaf' structure was independently proposed in several publications and finalized following X-ray crystallography in 1974.
Ribosomal RNA was discovered next, followed by URNA in the early 1980s. Since then, discoveries have continued with snoRNAs, Xist, CRISPR, riboswitches, and miRNA. The discovery of the RNAi mechanism associated with miRNA earned Craig C. Mello and Andrew Fire the 2006 Nobel Prize in Physiology or Medicine. Recent discoveries have been achieved through both experimental and bioinformatic methods.
Reader's Guide
Non-coding RNAs belong to several groups and are involved in many cellular processes, ranging from conserved ncRNAs across all cellular life to transient ncRNAs specific to a few species. Conserved ncRNAs are thought to be molecular fossils from the RNA world, with current roles mostly in regulating information flow from DNA to protein. In translation, ribosomes consist of more than 60% ribosomal RNA, catalyzing translation, while tRNAs act as adaptor molecules. snoRNAs guide covalent modifications of rRNA, tRNA, and snRNAs; RNase P matures tRNA sequences; and SRP transports nascent proteins. In RNA splicing, the spliceosome contains ncRNA components such as U1, U2, U4, U5, and U6 for the major form, and U11, U12, U5, U4atac, and U6atac for the minor form. Self-splicing RNAs (group I and II catalytic introns) excise themselves. In DNA replication, Y RNAs are necessary for replication through interactions with chromatin. In gene regulation, microRNAs down-regulate expression by binding to mRNA 3' UTRs; 7SK RNA negatively regulates Pol II elongation factor P-TEFb; bacterial 6S RNA represses sigma70-dependent promoters; OxyS RNA represses translation by occluding ribosome binding; and B2 RNA represses mRNA transcription in response to heat shock. The act of transcription of ncRNA can influence chromatin remodeling.
Did You Know?
- The first non-coding RNA characterized was an alanine tRNA from baker's yeast, published in 1965.
- Ribosomes consist of more than 60% ribosomal RNA, which catalyzes translation.
- The discovery of the RNAi mechanism associated with miRNA earned Craig C. Mello and Andrew Fire the 2006 Nobel Prize.
- There is no consensus on how much non-coding transcription is functional; some believe most ncRNAs are 'junk RNA'.
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