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==Key discoveries in RNA biology== {{further|History of RNA biology}} [[File:R Holley.jpg|thumb|210px|Robert W. Holley, left, poses with his research team.]] Research on RNA has led to many important biological discoveries and numerous [[Nobel Prize]]s. [[Nucleic acid]]s were discovered in 1868 by [[Friedrich Miescher]], who called the material 'nuclein' since it was found in the [[Cell nucleus|nucleus]].<ref>{{cite journal | vauthors = Dahm R | title = Friedrich Miescher and the discovery of DNA | journal = Developmental Biology | volume = 278 | issue = 2 | pages = 274–88 | date = February 2005 | pmid = 15680349 | doi = 10.1016/j.ydbio.2004.11.028 | doi-access = }}</ref> It was later discovered that [[Prokaryote|prokaryotic]] cells, which do not have a nucleus, also contain nucleic acids. The role of RNA in protein synthesis was suspected already in 1939.<ref>{{cite journal|journal=Nature | vauthors = Caspersson T, Schultz J | title = Pentose nucleotides in the cytoplasm of growing tissues|date=1939|volume=143|doi=10.1038/143602c0|pages=602–03|issue=3623|bibcode=1939Natur.143..602C| s2cid = 4140563 }}</ref> [[Severo Ochoa]] won the 1959 [[Nobel Prize in Medicine]] (shared with [[Arthur Kornberg]]) after he discovered an enzyme that can synthesize RNA in the laboratory.<ref>{{cite web | vauthors = Ochoa S | title = Enzymatic synthesis of ribonucleic acid|work=Nobel Lecture|date=1959|url=http://nobelprize.org/nobel_prizes/medicine/laureates/1959/ochoa-lecture.pdf}}</ref> However, the enzyme discovered by Ochoa ([[polynucleotide phosphorylase]]) was later shown to be responsible for RNA degradation, not RNA synthesis. In 1956 Alex Rich and David Davies hybridized two separate strands of RNA to form the first crystal of RNA whose structure could be determined by X-ray crystallography.<ref>{{cite journal | vauthors = Rich A, Davies D |title=A New Two-Stranded Helical Structure: Polyadenylic Acid and Polyuridylic Acid|journal=Journal of the American Chemical Society|date=1956|volume=78|issue=14|doi=10.1021/ja01595a086|pages=3548–49}}</ref> The sequence of the 77 nucleotides of a yeast tRNA was found by [[Robert W. Holley]] in 1965,<ref>{{cite journal | vauthors = Holley RW, Apgar J, Everett GA, Madison JT, Marquisee M, Merrill SH, Penswick JR, Zamir A | title = Structure of a ribonucleic acid | journal = Science | volume = 147 | issue = 3664 | pages = 1462–65 | date = March 1965 | pmid = 14263761 | doi = 10.1126/science.147.3664.1462 | bibcode = 1965Sci...147.1462H | s2cid = 40989800 | display-authors = 1 }}</ref> winning Holley the [[List of Nobel laureates in Physiology or Medicine|1968 Nobel Prize in Medicine]] (shared with [[Har Gobind Khorana]] and [[Marshall Nirenberg]]). In the early 1970s, [[retrovirus]]es and [[reverse transcriptase]] were discovered, showing for the first time that enzymes could copy RNA into DNA (the opposite of the usual route for transmission of genetic information). For this work, [[David Baltimore]], [[Renato Dulbecco]] and [[Howard Temin]] were awarded a Nobel Prize in 1975. In 1976, [[Walter Fiers]] and his team determined the first complete nucleotide sequence of an RNA virus genome, that of [[bacteriophage MS2]].<ref>{{cite journal | vauthors = Fiers W, Contreras R, Duerinck F, Haegeman G, Iserentant D, Merregaert J, Min Jou W, Molemans F, Raeymaekers A, Van den Berghe A, Volckaert G, Ysebaert M | title = Complete nucleotide sequence of bacteriophage MS2 RNA: primary and secondary structure of the replicase gene | journal = Nature | volume = 260 | issue = 5551 | pages = 500–07 | date = April 1976 | pmid = 1264203 | doi = 10.1038/260500a0 | bibcode = 1976Natur.260..500F | s2cid = 4289674 | display-authors = 1 }}</ref> In 1977, [[intron]]s and [[RNA splicing]] were discovered in both mammalian viruses and in cellular genes, resulting in a 1993 Nobel to [[Philip A. Sharp|Philip Sharp]] and [[Richard J. Roberts|Richard Roberts]]. Catalytic RNA molecules ([[ribozyme]]s) were discovered in the early 1980s, leading to a 1989 Nobel award to [[Thomas Cech]] and [[Sidney Altman]]. In 1990, it was found in ''[[Petunia]]'' that introduced genes can silence similar genes of the plant's own, now known to be a result of [[RNA interference]].<ref>{{cite journal | vauthors = Napoli C, Lemieux C, Jorgensen R | title = Introduction of a Chimeric Chalcone Synthase Gene into Petunia Results in Reversible Co-Suppression of Homologous Genes in trans | journal = The Plant Cell | volume = 2 | issue = 4 | pages = 279–89 | date = April 1990 | pmid = 12354959 | pmc = 159885 | doi = 10.1105/tpc.2.4.279 }}</ref><ref>{{cite journal | vauthors = Dafny-Yelin M, Chung SM, Frankman EL, Tzfira T | title = pSAT RNA interference vectors: a modular series for multiple gene down-regulation in plants | journal = Plant Physiology | volume = 145 | issue = 4 | pages = 1272–81 | date = December 2007 | pmid = 17766396 | pmc = 2151715 | doi = 10.1104/pp.107.106062 }}</ref> At about the same time, 22 nt long RNAs, now called [[microRNA]]s, were found to have a role in the [[developmental biology|development]] of ''[[Caenorhabditis elegans|C. elegans]]''.<ref>{{cite journal | vauthors = Ruvkun G | s2cid = 83506718 | title = Molecular biology. Glimpses of a tiny RNA world | journal = Science | volume = 294 | issue = 5543 | pages = 797–99 | date = October 2001 | pmid = 11679654 | doi = 10.1126/science.1066315 }}</ref> Studies on RNA interference earned a Nobel Prize for [[Andrew Z. Fire|Andrew Fire]] and [[Craig Mello]] in 2006, and another Nobel for studies on the transcription of RNA to [[Roger Kornberg]] in the same year. The discovery of gene regulatory RNAs has led to attempts to develop drugs made of RNA, such as [[siRNA]], to silence genes.<ref>{{cite journal | vauthors = Fichou Y, Férec C | title = The potential of oligonucleotides for therapeutic applications | journal = Trends in Biotechnology | volume = 24 | issue = 12 | pages = 563–70 | date = December 2006 | pmid = 17045686 | doi = 10.1016/j.tibtech.2006.10.003 }}</ref> Adding to the Nobel prizes for research on RNA, in 2009 it was awarded for the elucidation of the atomic structure of the ribosome to [[Venki Ramakrishnan]], [[Thomas A. Steitz]], and [[Ada Yonath]]. In 2023 the [[Nobel Prize in Physiology or Medicine]] was awarded to [[Katalin Karikó]] and [[Drew Weissman]] for their discoveries concerning [[Nucleoside analogue|modified nucleosides]] that enabled the development of effective mRNA vaccines against COVID-19.<ref>{{Cite web |title=The Nobel Prize in Physiology or Medicine 2023 |url=https://www.nobelprize.org/prizes/medicine/2023/press-release/ |access-date=2023-10-03 |website=NobelPrize.org |language=en-US}}</ref><ref>{{Cite news |date=2023-10-02 |title=Hungarian and US scientists win Nobel for COVID-19 vaccine discoveries |language=en |work=Reuters |url=https://www.reuters.com/article/nobel-prize-medicine-idCAKCN3120KJ |access-date=2023-10-03}}</ref><ref>{{Cite web |title=The Nobel Prize in Physiology or Medicine 2023 |url=https://www.nobelprize.org/prizes/medicine/2023/kariko/facts/ |access-date=2023-10-03 |website=NobelPrize.org |language=en-US}}</ref> === Relevance for prebiotic chemistry and abiogenesis === In 1968, [[Carl Woese]] hypothesized that RNA might be catalytic and suggested that the earliest forms of life (self-replicating molecules) could have relied on RNA both to carry genetic information and to catalyze biochemical reactions—an [[RNA world hypothesis|RNA world]].<ref>{{cite web|url=http://deposit.ddb.de/cgi-bin/dokserv?idn=982323891&dok_var=d1&dok_ext=pdf&filename=982323891.pdf|title=Common sequence structure properties and stable regions in RNA secondary structures|date=2006|work=Dissertation, Albert-Ludwigs-Universität, Freiburg im Breisgau|page=1|archive-url=https://web.archive.org/web/20120309212648/http://deposit.ddb.de/cgi-bin/dokserv?idn=982323891&dok_var=d1&dok_ext=pdf&filename=982323891.pdf|archive-date=March 9, 2012|url-status=dead|vauthors=Siebert S}}</ref><ref>{{cite journal | vauthors = Szathmáry E | title = The origin of the genetic code: amino acids as cofactors in an RNA world | journal = Trends in Genetics | volume = 15 | issue = 6 | pages = 223–29 | date = June 1999 | pmid = 10354582 | doi = 10.1016/S0168-9525(99)01730-8 }}</ref> In May 2022, scientists discovered that RNA can form spontaneously on prebiotic [[Volcanic glass|basalt lava glass]], presumed to have been abundant on the [[early Earth]].<ref name="AST-20220519">{{cite journal |author=Jerome, Craig A. |display-authors=et al. |title=Catalytic Synthesis of Polyribonucleic Acid on Prebiotic Rock Glasses |date=19 May 2022 |journal=[[Astrobiology (journal)|Astrobiology]] |volume=22 |issue=6 |pages=629–636 |doi=10.1089/ast.2022.0027 |pmid=35588195 |pmc=9233534 |bibcode=2022AsBio..22..629J |s2cid=248917871 }}</ref><ref name="PO-20220603">{{cite news |author=Foundation for Applied Molecular Evolution |title=Scientists announce a breakthrough in determining life's origin on Earth—and maybe Mars |url=https://phys.org/news/2022-06-scientists-breakthrough-life-earthand-mars.html |date=3 June 2022 |work=[[Phys.org]] |accessdate=3 June 2022 }}</ref> In March 2015, [[DNA]] and RNA [[nucleobase]]s, including [[uracil]], [[cytosine]] and [[thymine]], were reportedly formed in the laboratory under [[outer space]] conditions, using starter chemicals such as [[pyrimidine]], an [[organic compound]] commonly found in [[meteorite]]s. [[Pyrimidine]], like [[polycyclic aromatic hydrocarbons]] (PAHs), is one of the most carbon-rich compounds found in the [[universe]] and may have been formed in [[red giant]]s or in [[Cosmic dust|interstellar dust]] and gas clouds.<ref name="NASA-20150303">{{cite web|url=http://www.nasa.gov/content/nasa-ames-reproduces-the-building-blocks-of-life-in-laboratory|title=NASA Ames Reproduces the Building Blocks of Life in Laboratory|last=Marlaire|first=Ruth|name-list-style=vanc|date=3 March 2015|work=[[NASA]]|access-date=5 March 2015|archive-date=5 March 2015|archive-url=https://web.archive.org/web/20150305083306/http://www.nasa.gov/content/nasa-ames-reproduces-the-building-blocks-of-life-in-laboratory/|url-status=dead}}</ref> In July 2022, astronomers reported massive amounts of [[Abiogenesis#Producing molecules: prebiotic synthesis|prebiotic molecule]]s, including possible RNA precursors, in the [[Galactic Center|galactic center]] of the [[Milky Way Galaxy]].<ref name="SA-20220708">{{cite news |last=Starr |first=Michelle |title=Loads of Precursors For RNA Have Been Detected in The Center of Our Galaxy |url=https://www.sciencealert.com/scientists-have-found-a-bunch-of-rna-precursors-in-the-galactic-center |date=8 July 2022 |work=[[ScienceAlert]] |accessdate=9 July 2022 }}</ref><ref name="FASS-20220708">{{cite journal |author=Rivilla, Victor M. |display-authors=et al. |title=Molecular Precursors of the RNA-World in Space: New Nitriles in the G+0.693–0.027 Molecular Cloud |date=8 July 2022 |journal=[[Frontiers in Astronomy and Space Sciences]] |volume=9 |page=876870 |doi=10.3389/fspas.2022.876870 |arxiv=2206.01053 |bibcode=2022FrASS...9.6870R |doi-access=free }}</ref>
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