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Non-coding RNA
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==History and discovery== {{further|History of molecular biology}} [[Nucleic acid]]s were first discovered in 1868 by [[Friedrich Miescher]],<ref>{{cite journal | vauthors = Dahm R | title = Friedrich Miescher and the discovery of DNA | journal = Developmental Biology | volume = 278 | issue = 2 | pages = 274β288 | date = February 2005 | pmid = 15680349 | doi = 10.1016/j.ydbio.2004.11.028 }}</ref> and by 1939, RNA had been implicated in [[protein biosynthesis|protein synthesis]].<ref>{{cite journal | journal=Nature | vauthors = Caspersson T, Schultz J | title = Pentose nucleotides in the cytoplasm of growing tissues | year = 1939 | volume = 143 | doi = 10.1038/143602c0 | pages =602β3 | issue = 3623 | bibcode = 1939Natur.143..602C | s2cid = 4140563 }}</ref> Two decades later, [[Francis Crick]] predicted a functional RNA component which mediated [[translation (genetics)|translation]]; he reasoned that RNA is better suited to base-pair with an mRNA transcript than a pure [[polypeptide]].<ref>{{cite journal | vauthors = Crick FH | title = On protein synthesis | journal = Symposia of the Society for Experimental Biology | volume = 12 | pages = 138β163 | year = 1958 | pmid = 13580867 }}</ref> [[Image:TRNA-Phe yeast 1ehz.png|thumb|250px|The cloverleaf structure of Yeast tRNA<sup>Phe</sup> (''inset'') and the 3D structure determined by X-ray analysis.]] The first non-coding RNA to be characterised was an [[alanine]] tRNA found in [[baker's yeast]], its structure was published in 1965.<ref name="Hol65">{{cite journal | vauthors = Holley RW, Apgar J, Everett GA, Madison JT, Marquisee M, Merrill SH, Penswick JR, Zamir A | display-authors = 6 | title = Structure of a Ribonucleic Acid | journal = Science | volume = 147 | issue = 3664 | pages = 1462β1465 | date = March 1965 | pmid = 14263761 | doi = 10.1126/science.147.3664.1462 | s2cid = 40989800 | bibcode = 1965Sci...147.1462H }}</ref> To produce a purified alanine tRNA sample, [[Robert W. Holley]] ''et al.'' used 140[[kilogram|kg]] of commercial baker's yeast to give just 1[[gram|g]] of purified tRNA<sup>Ala</sup> for analysis.<ref name="Nobel68">{{cite web | url = http://nobelprize.org/nobel_prizes/medicine/laureates/1968/index.html | title = The Nobel Prize in Physiology or Medicine 1968 | access-date = 2007-07-28 | publisher = Nobel Foundation}}</ref> 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.<ref name="Nobel68" /> Of the three structures originally proposed for this tRNA,<ref name="Hol65" /> the 'cloverleaf' structure was independently proposed in several following publications.<ref name="pmid5938777">{{cite journal | vauthors = Madison JT, Everett GA, Kung H | title = Nucleotide sequence of a yeast tyrosine transfer RNA | journal = Science | volume = 153 | issue = 3735 | pages = 531β534 | date = July 1966 | pmid = 5938777 | doi = 10.1126/science.153.3735.531 | s2cid = 9265016 | citeseerx = 10.1.1.1001.2662 | bibcode = 1966Sci...153..531M }}</ref><ref>{{cite journal | vauthors = Zachau HG, DΓΌtting D, Feldmann H, Melchers F, Karau W | title = Serine specific transfer ribonucleic acids. XIV. Comparison of nucleotide sequences and secondary structure models | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 31 | pages = 417β424 | year = 1966 | pmid = 5237198 | doi = 10.1101/SQB.1966.031.01.054 }}</ref><ref>{{cite journal | vauthors = Dudock BS, Katz G, Taylor EK, Holley RW | title = Primary structure of wheat germ phenylalanine transfer RNA | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 62 | issue = 3 | pages = 941β945 | date = March 1969 | pmid = 5257014 | pmc = 223689 | doi = 10.1073/pnas.62.3.941 | doi-access = free | bibcode = 1969PNAS...62..941D }}</ref><ref>{{cite journal | vauthors = Cramer F, Doepner H, Haar F VD, Schlimme E, Seidel H | title = On the conformation of transfer RNA | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 61 | issue = 4 | pages = 1384β1391 | date = December 1968 | pmid = 4884685 | pmc = 225267 | doi = 10.1073/pnas.61.4.1384 | doi-access = free | bibcode = 1968PNAS...61.1384C }}</ref> The cloverleaf [[secondary structure]] was finalised following [[X-ray crystallography]] analysis performed by two independent research groups in 1974.<ref>{{cite journal | vauthors = Ladner JE, Jack A, Robertus JD, Brown RS, Rhodes D, Clark BF, Klug A | title = Structure of yeast phenylalanine transfer RNA at 2.5 A resolution | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 72 | issue = 11 | pages = 4414β4418 | date = November 1975 | pmid = 1105583 | pmc = 388732 | doi = 10.1073/pnas.72.11.4414 | doi-access = free | bibcode = 1975PNAS...72.4414L }}</ref><ref>{{cite journal | vauthors = Kim SH, Quigley GJ, Suddath FL, McPherson A, Sneden D, Kim JJ, Weinzierl J, Rich A | display-authors = 6 | title = Three-dimensional structure of yeast phenylalanine transfer RNA: folding of the polynucleotide chain | journal = Science | volume = 179 | issue = 4070 | pages = 285β288 | date = January 1973 | pmid = 4566654 | doi = 10.1126/science.179.4070.285 | s2cid = 28916938 | bibcode = 1973Sci...179..285K }}</ref> [[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.<ref name="Edd01">{{cite journal | vauthors = Eddy SR | title = Non-coding RNA genes and the modern RNA world | journal = Nature Reviews. Genetics | volume = 2 | issue = 12 | pages = 919β929 | date = December 2001 | pmid = 11733745 | doi = 10.1038/35103511 | s2cid = 18347629 }}</ref> Recent notable additions include [[riboswitch]]es and [[miRNA]]; the discovery of the RNAi [[mechanism (biology)|mechanism]] associated with the latter earned [[Craig C. Mello]] and [[Andrew Fire]] the 2006 [[Nobel Prize in Physiology or Medicine]].<ref>{{cite web | title=Advanced Information: RNA interference | vauthors = Daneholt B | work=The Nobel Prize in Physiology or Medicine 2006 | url=http://nobelprize.org/nobel_prizes/medicine/laureates/2006/adv.html | access-date=2007-01-25 | archive-url=https://web.archive.org/web/20070120113455/http://nobelprize.org/nobel_prizes/medicine/laureates/2006/adv.html <!--Added by H3llBot--> | archive-date=2007-01-20}}</ref> Recent discoveries of ncRNAs have been achieved through both experimental and [[Bioinformatics discovery of non-coding RNAs|bioinformatic methods]].
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