RNA 25758 225353971 2008-07-13T06:47:22Z Narayanese 1324750 /* Structure */ {{otheruses}} [[Image:Pre-mRNA-1ysv.png|thumb|200px|A hairpin loop from a pre-mRNA. Notice its nitrogen-rich (blue) bases and oxygen-rich (red) backbone.]] '''Ribonucleic acid''' ('''RNA''') is a [[nucleic acid]] and consists of a long chain of [[nucleotide]] units. Each nucleotide consists of a [[nucleobase|nitrogenous base]], a [[ribose]] sugar, and a [[phosphate]]. RNA is very similar to [[DNA]], but differs in a few important structural details: in the cell RNA is usually single stranded, while DNA is usually double stranded. RNA nucleotides contain ribose while DNA contains [[deoxyribose]] (a type of ribose that lacks one oxygen atom), and RNA has the nucleotide [[uracil]] rather than [[thymine]] which is present in DNA. RNA is [[Transcription (genetics)|transcribed]] from DNA by [[enzyme]]s called [[RNA polymerase]]s and is generally further processed by other enzymes. RNA is central to the synthesis of [[protein]]s. Here, a type of RNA called [[messenger RNA]] carries information from DNA to structures called [[ribosome]]s. These ribosomes are made from proteins and ribosomal RNAs, which come together to form a molecular machine that can read messenger RNAs and [[Translation (biology)|translate]] the information they carry into proteins. There are also many RNAs involved in modifying other RNAs; some of it causing maturation of RNAs, other resulting in altered expression or products of [[gene]]s. ==Structure== [[Image:Piwi-siRNA-basepairing.png|thumb|right|230px|Watson-Crick base pairs in a [[siRNA]] (hydrogen atoms are not shown)]] Each nucleotide in RNA contains a ribose sugar, with carbons numbered 1' through 5'. A base is attached to the 1' position, generally [[adenine]] (A), [[cytosine]] (C), [[guanine]] (G) or [[uracil]] (U). Adenine and guanine are [[purine]]s, cytosine and uracil are [[pyrimidine]]s. A [[phosphate]] group is attached to the 3' position of one ribose and the 5' position of the next. The phosphate groups have a negative charge each at physiological pH, making RNA a charged molecule (polyanion). The bases may form [[hydrogen bond]]s between cytosine and guanine, between adenine and uracil and between guanine and uracil.<ref name="pmid15561141"/> However other interactions are possible, such as a group of adenine bases binding to each other in a bulge,<ref>{{cite book | title=RNA biochemistry and biotechnology| author=Barciszewski J, Frederic B, Clark C| date=1999| pages=73–87| publisher=Springer| isbn=0792358627}}</ref> or the GNRA [[tetraloop]] that has a guanine–adenine base-pair.<ref name="pmid15561141">{{cite journal | author = Lee JC, Gutell RR | title = Diversity of base-pair conformations and their occurrence in rRNA structure and RNA structural motifs | journal = J. Mol. Biol. | volume = 344 | issue = 5 | pages = 1225–49 | year = 2004 | doi = 10.1016/j.jmb.2004.09.072| pmid=15561141}}</ref> [[Image:RNA chemical structure.GIF|thumb|left|Chemical structure of RNA]] An important structural feature of RNA that distinguishes it from DNA is the presence of a [[hydroxyl]] group at the 2' position of the ribose sugar. The presence of this functional group causes the helix to adopt the [[A-DNA|A-form geometry]] rather than the B-form most commonly observed in DNA.<ref>{{cite journal | author=Salazar M, Fedoroff OY, Miller JM, Ribeiro NS, Reid BR| title=The DNA strand in DNAoRNA hybrid duplexes is neither B-form nor A-form in solution| journal=Biochemistry| year=1992| volume=32| issue=16| pages=4207–15| pmid=7682844| doi=10.1021/bi00067a007}}</ref> This results in a very deep and narrow major groove and a shallow and wide minor groove.<ref>{{cite journal | author=Hermann T, Patel DJ| title=RNA bulges as architectural and recognition motifs| journal=Structure| year=2000| volume=8| issue=3| pages=R47–R54| doi=10.1016/S0969-2126(00)00110-6 | pages = R47 | pmid = 10745015 }}</ref> A second consequence of the presence of the 2'-hydroxyl group is that in conformationally flexible regions of an RNA molecule (that is, not involved in formation of a double helix), it can chemically attack the adjacent phosphodiester bond to cleave the backbone.<ref>{{cite journal | author=Mikkola S, Nurmi K, Yousefi-Salakdeh E, Strömberg R, Lönnberg H| title=The mechanism of the metal ion promoted cleavage of RNA phosphodiester bonds involves a general acid catalysis by the metal aquo ion on the departure of the leaving group| journal=Perkin transactions 2| year=1999| pages=1619–26| doi=10.1039/a903691a}}</ref> RNA is transcribed with only four bases (adenine, cytosine, guanine and uracil),<ref>{{cite book | title=Clinical gene analysis and manipulation: tools, techniques and troubleshooting | author=Jankowski JAZ, Polak JM| date=1996| pages=14| publisher=Cambridge University Press| isbn=0521478960}}</ref> but there are numerous modified bases and sugars in mature RNAs. [[Pseudouridine]] (Ψ), in which the linkage between uracil and ribose is changed from a C–N bond to a C–C bond, and ribothymidine (T), are found in various places (most notably in the TΨC loop of [[tRNA]]).<ref>{{cite journal | author=Yu Q, Morrow CD| title=Identification of critical elements in the tRNA acceptor stem and TΨC loop necessary for human immunodeficiency virus type 1 infectivity| journal=J Virol.| year=2001| volume=75| issue=10| pages=4902–6| doi=10.1128/JVI.75.10.4902-4906.2001 | pmid = 11312362 }}</ref> Another notable modified base is hypoxanthine, a deaminated adenine base whose [[nucleoside]] is called [[inosine]]. Inosine plays a key role in the [[wobble hypothesis]] of the [[genetic code]].<ref>{{cite journal | author=Elliott MS, Trewyn RW| title=Inosine biosynthesis in transfer RNA by an enzymatic insertion of hypoxanthine| journal=J. Biol. Chem.| year=1983| volume=259| issue=4| pages=2407–10| pmid=6365911}}</ref> There are nearly 100 other naturally occurring modified nucleosides,<ref>{{cite book | title=tRNA: Structure, biosynthesis, and function | author=Söll D, RajBhandary U| date=1995| pages=165| publisher=ASM Press| isbn=155581073X}}</ref> of which pseudouridine and nucleosides with [[2'-O-methylation|2'-O-methylribose]] are the most common.<ref>{{cite journal | author=Kiss T| title=Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs| journal=The EMBO Journal | year=2001| volume=20| pages=3617–22| doi=10.1093/emboj/20.14.3617 | pmid = 11447102 }}</ref> The specific roles of many of these modifications in RNA are not fully understood. However, it is notable that in ribosomal RNA, many of the post-transcriptional modifications occur in highly functional regions, such as the peptidyl transferase center and the subunit interface, implying that they are important for normal function.<ref>{{cite journal | author=King TH, Liu B, McCully RR, Fournier MJ| title=Ribosome structure and activity are altered in cells lacking snoRNPs that form pseudouridines in the peptidyl transferase center | journal=Molecular Cell| year=2002| volume=11| issue=2| pages=425–35| doi=10.1016/S1097-2765(03)00040-6 | pmid = 12620230}}</ref> [[Image:Ciliate telomerase RNA.JPG|thumb|Secondary structure of a [[telomerase RNA]]]] The functional form of single stranded RNA molecules, just like proteins, frequently requires a specific tertiary structure. The scaffold for this structure is provided by secondary structural elements which are hydrogen bonds within the molecule. This leads to several recognizable "domains" of secondary structure like [[hairpin loop]]s, bulges and internal loops.<ref>{{cite journal | author=Mathews DH, Disney MD, Childs JL, Schroeder SJ, Zuker M, Turner DH| title=Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure| journal=Proc. Natl. Acad. Sci. USA| year=2004| volume=101| issue=19| pages=7287–92| doi=10.1073/pnas.0401799101 | pmid = 15123812}}</ref> Since RNA is charged, metal ions such as [[Magnesium|Mg<sup>2+</sup>]] are needed to stabilise many secondary structures.<ref>{{cite journal |author=Tan ZJ, Chen SJ |title=Salt dependence of nucleic acid hairpin stability |journal=Biophys. J. |volume=95 |pages=738–52 |year=2008 |pmid=18424500 |doi=10.1529/biophysj.108.131524}}</ref> ==Comparison with DNA== RNA and [[DNA]] differ in three main ways. First, unlike DNA which is double-stranded, RNA is a single-stranded molecule in most of its biological roles and has a much shorter chain of nucleotides. Second, while DNA contains ''deoxyribose'', RNA contains ''ribose'', (there is no hydroxyl group attached to the pentose ring in the [[nucleic acid nomenclature|2']] position in DNA). These hydroxyl groups make RNA less stable than DNA because it is more prone to [[hydrolysis]]. Third, the complementary nucleotide to [[adenine]] is not [[thymine]], as it is in DNA, but rather [[uracil]], which is an [[methylation|unmethylated]] form of thymine.<ref name=Biochemistry/> [[Image:Ribosome 50s.png|thumb|The [[50S]] ribosomal subunit. RNA is in orange, protein in blue. The active site is in the middle (red).]] Like DNA, most biologically active RNAs including tRNA, rRNA, snRNAs and other, non-coding, RNAs are extensively base paired to form double stranded helices. Structural analysis of these RNAs have revealed that they are highly structured. Unlike DNA, this structure is not long double-stranded helices but rather collections of short helices packed together into structures akin to proteins. In this fashion, RNAs can achieve chemical [[catalysis]], like enzymes.<ref>{{cite journal | author=Higgs PG| title=RNA secondary structure: physical and computational aspects| journal=Quarterly Reviews of Biophysics| year=2000| volume=33| pages=199–253| doi=10.1017/S0033583500003620 | pmid = 11191843 }}</ref> For instance, determination of the structure of the ribosome&mdash;an enzyme that catalyzes peptide bond formation&mdash;revealed that its active site is composed entirely of RNA.<ref name=ribosome_activity>{{cite journal | author=Nissen P, Hansen J, Ban N, Moore PB, Steitz TA | title=The structural basis of ribosome activity in peptide bond synthesis | journal=Science| year=2000| volume=289| issue=5481| pages=920–30| doi=10.1126/science.289.5481.920 | pmid = 10937990}}</ref> ==Synthesis== Synthesis of RNA is usually catalyzed by an enzyme&mdash;[[RNA polymerase]]&mdash;using DNA as a template, a process known as [[Transcription (genetics)|transcription]]. Initiation of transcription begins with the binding of the enzyme to a [[promoter]] sequence in the DNA (usually found "upstream" of a gene). The DNA double helix is unwound by the [[helicase]] activity of the enzyme. The enzyme then progresses along the template strand in the 3’ to 5’ direction, synthesizing a complementary RNA molecule with elongation occurring in the 5’ to 3’ direction. The DNA sequence also dictates where termination of RNA synthesis will occur.<ref>{{cite journal | author=Nudler E, Gottesman ME| title=Transcription termination and anti-termination in E. coli | journal=Genes to Cells| year=2002| volume=7| pages=755–68| doi=10.1046/j.1365-2443.2002.00563.x | pmid = 12167155 }}</ref> RNAs are often [[Post-transcriptional modification|modified]] by enzymes after transcription. For example, a [[poly(A) tail]] and a [[5' cap]] are added to eukaryotic [[pre-mRNA]]. There are also a number of [[RNA-dependent RNA polymerase]]s that use RNA as their template for synthesis of a new strand of RNA. For instance, a number of RNA viruses (such as poliovirus) use this type of enzyme to replicate their genetic material.<ref>{{cite journal | author=Jeffrey L Hansen, Alexander M Long, Steve C Schultz| title=Structure of the RNA-dependent RNA polymerase of poliovirus | journal=Structure| year=1997| volume=5| issue=8| pages=1109-22 | doi=10.1016/S0969-2126(97)00261-X | pmid = 9309225 }}</ref> Also, it is known that RNA-dependent RNA polymerases are required for the [[RNA interference]] pathway in many organisms.<ref>{{cite journal | author=Ahlquist P| title=RNA-Dependent RNA Polymerases, Viruses, and RNA Silencing | journal=Science| year=2002| volume=296| issue=5571| pages=1270–73| doi=10.1126/science.1069132 | pmid = 12016304 }}</ref> ==Types of RNA== {{seealso|List of RNAs}} ===Overview=== [[Image:Full length hammerhead ribozyme.png|thumb|upright|Structure of a [[hammerhead ribozyme]], a ribozyme that cuts RNA]] Messenger RNA (mRNA) is the RNA that carries information from DNA to the [[ribosome]], the sites of protein synthesis ([[Translation (biology)|translation]]) in the cell. The coding sequence of the mRNA determines the [[amino acid]] sequence in the [[protein]] that is produced.<ref name=The_Cell/> Many RNAs do not code for protein however. These [[non-coding RNA]]s can be encoded by their own genes (RNA genes), but can also derive from mRNA [[intron]]s.<ref name=transcriptome/> The most prominent examples of non-coding RNAs are [[transfer RNA]] (tRNA) and [[ribosomal RNA]] (rRNA), both of which are involved in the process of translation.<ref name=Biochemistry>{{cite book |author=Berg JM, Tymoczko JL, Stryer L |title= Biochemistry | edition=5th edition |pages =118–19, 781–808 | publisher= WH Freeman and Company |year=2002 |isbn= 0-7167-4684-0}}</ref> There are also non-coding RNAs involved in gene regulation, [[RNA processing]] and other roles. Certain RNAs are able to [[catalysis|catalyse]] chemical reactions such as cutting and [[ligase|ligating]] other RNA molecules,<ref>{{cite journal | author=Rossi JJ| title=Ribozyme diagnostics comes of age | journal=Chemistry & Biology| year=2004| volume=11| issue=7| pages=894–95 | doi=10.1016/j.chembiol.2004.07.002}}</ref> and the catalysis of [[peptide bond]] formation in the [[ribosome]];<ref name=ribosome_activity/> these are known as [[ribozyme]]s. ===In translation=== [[Messenger RNA]] (mRNA) carries information about a protein sequence to the [[ribosome]]s, the protein synthesis factories in the cell. It is [[genetic code|coded]] so that every three nucleotides (a codon) correspond to one amino acid. In [[eukaryotic]] cells, once precursor mRNA (pre-mRNA) has been transcribed from DNA, it is processed to mature mRNA. This removes its [[intron]]s&mdash;non-coding sections of the pre-mRNA. The mRNA is then exported from the nucleus to the cytoplasm, where it is bound to ribosomes and [[Translation (biology)|translated]] into its corresponding protein form with the help of [[tRNA]]. In prokaryotic cells, which do not have nucleus and cytoplasm compartments, mRNA can bind to ribosomes while it is being transcribed from DNA. After a certain amount of time the message degrades into its component nucleotides with the assistance of [[ribonuclease]]s.<ref name=The_Cell/> [[Transfer RNA]] (tRNA) is a small RNA chain of about 80 [[nucleotide]]s that transfers a specific amino acid to a growing [[polypeptide]] chain at the ribosomal site of protein synthesis during translation. It has sites for amino acid attachment and an [[anticodon]] region for [[codon]] recognition that binds to a specific sequence on the messenger RNA chain through hydrogen bonding.<ref name=transcriptome/> [[Ribosomal RNA]] (rRNA) is the catalytic component of the ribosomes. Eukaryotic ribosomes contain four different rRNA molecules: 18S, 5.8S, 28S and 5S rRNA. Three of the rRNA molecules are synthesized in the [[nucleolus]], and one is synthesized elsewhere. In the cytoplasm, ribosomal RNA and protein combine to form a nucleoprotein called a ribosome. The ribosome binds mRNA and carries out protein synthesis. Several ribosomes may be attached to a single mRNA at any time.<ref name=The_Cell>{{cite book | title=The Cell: A Molecular Approach| edition=3rd edition| author=Cooper GC, Hausman RE| date=2004| pages=261–76, 297, 339–44| publisher=Sinauer| isbn=0-87893-214-3}}</ref> rRNA is extremely abundant and makes up 80% of the 10&nbsp;mg/ml RNA found in a typical eukaryotic [[cytoplasm]].<ref>{{cite journal | author=Kampers T, Friedhoff P, Biernat J, Mandelkow E-M, Mandelkow E| title=RNA stimulates aggregation of microtubule-associated protein tau into Alzheimer-like paired helical filaments| journal=FEBS Letters| year=1996| volume=399 | pages = 104D| pmid=8985176 | doi = 10.1016/S0014-5793(96)01386-5 <!--Retrieved from CrossRef by DOI bot-->}}</ref> [[tmRNA|Transfer-messenger RNA]] (tmRNA) is found in many [[bacteria]] and [[plastid]]s. It tags proteins encoded by mRNAs that lack stop codons for degradation and prevents the ribosome from stalling.<ref>{{cite journal |author=Gueneau de Novoa P, Williams KP |title=The tmRNA website: reductive evolution of tmRNA in plastids and other endosymbionts |journal=Nucleic Acids Res. |volume=32 |issue=Database issue |pages=D104–8 |year=2004 |pmid=14681369 |doi=10.1093/nar/gkh102}}</ref> ===Regulatory RNAs=== Several types of RNA can downregulate gene expression by being complementary to a part of an mRNA or gene. [[MicroRNA]]s (miRNA; 21-22&nbsp;[[nucleotide|nt]]) are found in eukaryotes and act through [[RNA interference]] (RNAi), where an effector complex of miRNA and enzymes can break down mRNA which the miRNA is complementary to, block the mRNA from being translated, or accelerate its degradation.<ref>{{cite journal |author=Wu L, Belasco JG |title=Let me count the ways: mechanisms of gene regulation by miRNAs and siRNAs |journal=Mol. Cell |volume=29 |issue=1 |pages=1–7 |year=2008 |month=January |pmid=18206964 |doi=10.1016/j.molcel.2007.12.010}}</ref><ref>{{cite journal | author=Matzke MA, Matzke AJM | title=Planting the seeds of a new paradigm| journal=PLoS Biology | year=2004| volume=2| issue=5| pages=e133| doi=10.1371/journal.pbio.0020133 | pages = e133 | pmid = 15138502 }}</ref> While [[small interfering RNA]]s (siRNA; 20-25&nbsp;nt) are often produced by breakdown of viral RNA, there are also endogenous sources of siRNAs in plants.<ref>{{cite journal | author=Vazquez F, Vaucheret H, Rajagopalan R, Lepers C, Gasciolli V, Mallory AC, Hilbert J, Bartel DP, Crété P| title=Endogenous ''trans''-acting siRNAs regulate the accumulation of ''Arabidopsis'' mRNAs | journal=Molecular Cell| year=2004| volume=16| issue=1| pages= 69–79| doi=10.1016/j.molcel.2004.09.028 | pmid = 15469823 }}</ref> siRNAs act through RNA interference in a fashion similar to miRNAs. Some miRNAs and siRNAs upregulate genes instead ([[RNAa|RNA activation]]).<ref>{{cite journal | author=Doran G| title=RNAi – Is one suffix sufficient? | journal=Journal of RNAi and Gene Silencing | year=2007| volume=3| issue=1| pages=217–19 | url=http://libpubmedia.co.uk/RNAiJ-Issues/Issue-5/Doran.htm}}</ref><ref>{{cite journal |author=Pushparaj PN, Aarthi JJ, Kumar SD, Manikandan J |title=RNAi and RNAa - The Yin and Yang of RNAome |journal=Bioinformation |volume=2 |issue=6 |pages=235–7 |year=2008 |pmid=18317570 |pmc=2258431}}</ref> Animals have [[Piwi-interacting RNA]]s (piRNA; 29-30&nbsp;nt) which are active in [[germline]] cells and are thought to be a defense against [[transposon]]s and play a role in [[gametogenesis]].<ref name=fruitfly_piRNA>{{cite journal | author=Horwich MD, Li C Matranga C, Vagin V, Farley G, Wang P, Zamore PD| title=The ''Drosophila'' RNA methyltransferase, DmHen1, modifies germline piRNAs and single-stranded siRNAs in RISC| journal=Current Biology| year=2007| volume=17| pages=1265–72| doi=10.1016/j.cub.2007.06.030 | pmid = 17604629 }}</ref><ref>{{cite journal | author=Girard A, Sachidanandam R, Hannon GJ, Carmell MA| title=A germline-specific class of small RNAs binds mammalian Piwi proteins| journal=Nature| year=2006| volume=442| pages=199–202| doi=10.1038/nature04917 | pmid = 16751776}}</ref> [[Antisense RNA]]s are widespread among bacteria; most downregulate a gene, but a few are activators of transcription.<ref>{{cite journal | author=Wagner EG, Altuvia S, Romby P| title=Antisense RNAs in bacteria and their genetic elements| journal=Adv Genet.| year=2002| volume=46| pages=361–98| pmid=11931231| doi=10.1016/S0065-2660(02)46013-0}}</ref> Antisense RNA can act by binding to an mRNA, forming double-stranded RNA that is degraded by enzymes.<ref>{{cite book | author=Gilbert SF |title=Developmental Biology | edition=7th ed |publisher=Sinauer | isbn=0878932585 | pages=101–3 | year=2003}}</ref> There are many mRNA-like [[large non-coding RNA]]s that regulate genes in eukaryotes,<ref>{{cite journal |author=Hüttenhofer A, Schattner P, Polacek N |title=Non-coding RNAs: hope or hype? |journal=Trends Genet. |volume=21 |issue=5 |pages=289–97 |year=2005 |pmid=15851066 |doi=10.1016/j.tig.2005.03.007}}</ref> one such RNA is [[Xist]] which coats one X chromosome in female mammals and [[X-inactivation|inactivates]] it.<ref>{{cite journal | author=Heard E, Mongelard F, Arnaud D, Chureau C, Vourc'h C, Avner P| title=Human ''XIST'' yeast artificial chromosome transgenes show partial X inactivation center function in mouse embryonic stem cells | journal=Proc. Natl. Acad. Sci. USA| year=1999| volume=96| issue=12| pages=6841–46| pmid=10359800 | doi = 10.1073/pnas.96.12.6841}}</ref> An mRNA may contain regulatory elements itself, such as [[riboswitches]], in the [[Five prime untranslated region|5' UTR]] or [[Three prime untranslated region|3' UTR]]; these [[cis-regulatory element]]s regulate the activity of that mRNA.<ref>{{cite journal |author=Batey RT |title=Structures of regulatory elements in mRNAs |journal=Curr. Opin. Struct. Biol. |volume=16 |issue=3 |pages=299–306 |year=2006 |pmid=16707260 |doi=10.1016/j.sbi.2006.05.001}}</ref> ===In RNA processing=== [[Image:Uridine to pseudouridine.GIF|thumb|Uridine to pseudouridine is a common RNA modification.]] Many RNAs are involved in modifying other RNAs. [[Intron]]s are [[Splicing (genetics)|spliced]] out of [[pre-mRNA]] by [[spliceosome]]s, which contain several [[small nuclear RNA]]s (snRNA),<ref name=Biochemistry/> or the introns can be ribozymes that are spliced by themselves.<ref>{{cite journal |author=Steitz TA, Steitz JA |title=A general two-metal-ion mechanism for catalytic RNA |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=90 |issue=14 |pages=6498–502 |year=1993 |pmid=8341661 | doi = 10.1073/pnas.90.14.6498 <!--Retrieved from CrossRef by DOI bot-->}}</ref> RNA can also be altered by having its nucleotides modified to other nucleotides than [[adenosine|A]], [[cytidine|C]], [[guanosine|G]] and [[uridine|U]]. In eukaryotes, modifications of RNA nucleotides are generally directed by [[small nucleolar RNA]]s (snoRNA; 60-300&nbsp;nt),<ref name=transcriptome>{{cite book | title=Mining the transcriptome – methods and applications| url=http://www.diva-portal.org/diva/getDocument?urn_nbn_se_kth_diva-4115-3__fulltext.pdf| author=Wirta W| date=2006| isbn=91-7178-436-5}}</ref> found in the [[nucleolus]] and [[Cajal body|cajal bodies]]. snoRNAs associate with enzymes and guide them to a spot on an RNA by basepairing to that RNA. These enzymes then perform the nucleotide modification. rRNAs and tRNAs are extensively modified, but snRNAs and mRNAs can also be the target of base modification.<ref>{{cite journal |author=Xie J, Zhang M, Zhou T, Hua X, Tang L, Wu W |title=Sno/scaRNAbase: a curated database for small nucleolar RNAs and cajal body-specific RNAs |journal=Nucleic Acids Res. |volume=35 |pages=D183–7 |year=2007 |pmid=17099227 |doi=10.1093/nar/gkl873}}</ref><ref>{{cite journal | author=Omer AD, Ziesche S, Decatur WA, Fournier MJ, Dennis PP| title=RNA-modifying machines in archaea| journal=Molecular Microbiology| year=2003| volume=48| issue=3| pages=617–29| doi=10.1046/j.1365-2958.2003.03483.x | pmid = 12694609}}</ref> === RNA genomes === Like DNA, RNA can carry genetic information. [[RNA virus]]es have [[genome]]s composed of RNA, plus a variety of proteins encoded by that genome. The viral genome is replicated by some of those proteins, while other proteins protect the genome as the virus particle moves to a new host cell. [[Viroid]]s are another group of pathogens, but they consist only of RNA, do not encode any protein and are replicated by a host plant cell's polymerase.<ref>{{cite journal |author=Daròs JA, Elena SF, Flores R |title=Viroids: an Ariadne's thread into the RNA labyrinth |journal=EMBO Rep. |volume=7 |issue=6 |pages=593–8 |year=2006 |pmid=16741503 |doi=10.1038/sj.embor.7400706}}</ref> === In reverse transcription=== [[Reverse transcribing virus]]es replicate their genomes by [[Reverse transcription|reverse transcribing]] DNA copies from their RNA; these DNA copies are then transcribed to new RNA. [[Retrotransposon]]s also spread by copying DNA and RNA from one another,<ref>{{cite journal |author=Kalendar R, Vicient CM, Peleg O, Anamthawat-Jonsson K, Bolshoy A, Schulman AH |title=Large retrotransposon derivatives: abundant, conserved but nonautonomous retroelements of barley and related genomes |journal=Genetics |volume=166 |issue=3 | pages = D339 |year=2004 |pmid=15082561 | doi = 10.1534/genetics.166.3.1437 <!--Retrieved from CrossRef by DOI bot-->}}</ref> and [[telomerase]] contains an RNA that is used as template for building the ends of eukaryotic chromosomes.<ref>{{cite journal |author=Podlevsky JD, Bley CJ, Omana RV, Qi X, Chen JJ |title=The telomerase database |journal=Nucleic Acids Res. |volume=36 |issue=Database issue |pages=D339–43 |year=2008 |pmid=18073191 |doi=10.1093/nar/gkm700}}</ref> ===Double-stranded RNA=== Double-stranded RNA (dsRNA) is RNA with two complementary strands, similar to the DNA found in all cells. dsRNA forms the genetic material of some [[virus]]es ([[double-stranded RNA viruses]]). Double-stranded RNA such as viral RNA or [[siRNA]] can trigger [[RNA interference]] in [[eukaryote]]s, as well as [[interferon]] response in [[vertebrate]]s.<ref>{{cite journal | title=Four plant Dicers mediate viral small RNA biogenesis and DNA virus induced silencing| author=Blevins T ''et al''| journal=Nucleic Acids Res| year=2006| volume=34| issue=21| pages=6233–46| pmid=17090584 | doi = 10.1093/nar/gkl886 <!--Retrieved from CrossRef by DOI bot-->}}</ref><ref>{{cite journal |author=Jana S, Chakraborty C, Nandi S, Deb JK |title=RNA interference: potential therapeutic targets |journal=Appl. Microbiol. Biotechnol. |volume=65 |issue=6 |pages=649–57 |year=2004 |pmid=15372214 |doi=10.1007/s00253-004-1732-1}}</ref><ref>{{cite journal |author=Schultz U, Kaspers B, Staeheli P |title=The interferon system of non-mammalian vertebrates |journal=Dev. Comp. Immunol. |volume=28 |issue=5 |pages=499–508 |year=2004 |pmid=15062646 |doi=10.1016/j.dci.2003.09.009}}</ref> ==Discovery== [[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 | author=Dahm R| title=Friedrich Miescher and the discovery of DNA | journal=Developmental Biology | year=2005| volume=278| issue=2| pages=274–88 | pmid=15680349 | doi = 10.1016/j.ydbio.2004.11.028 <!--Retrieved from CrossRef by DOI bot-->}}</ref> It was later discovered that 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 | author=Caspersson T, Schultz J | title=Pentose nucleotides in the cytoplasm of growing tissues | year=1939 | volume=143 | doi=10.1038/143602c0 | pages=602–3}}</ref> [[Severo Ochoa]] won the 1959 [[Nobel Prize in Medicine]] after he discovered how RNA is synthesized.<ref>{{cite web | author=Ochoa S| title=Enzymatic synthesis of ribonucleic acid| work=Nobel Lecture |year=1959| url=http://nobelprize.org/nobel_prizes/medicine/laureates/1959/ochoa-lecture.pdf}}</ref> The sequence of the 77 nucleotides of a yeast tRNA was found by [[Robert W. Holley]] in 1965,<ref>{{cite journal | author=Holley RW ''et al''| title=Structure of a ribonucleic acid | journal=Science| year=1965| volume=147| issue=1664| pages=1462–65| doi=10.1126/science.147.3664.1462 | pmid = 14263761 }}</ref> winning Holley the 1968 Nobel Prize in Medicine. [[Carl Woese]] realised RNA can be catalytic in 1967 and proposed that the earliest forms of life relied on RNA both to carry genetic information and to catalyze biochemical reactions&mdash;an [[RNA world hypothesis|RNA world]].<ref>{{cite web | title=Common sequence structure properties and stable regions in RNA secondary structures| author=Siebert S| year=2006| pages=1| url=http://deposit.ddb.de/cgi-bin/dokserv?idn=982323891&dok_var=d1&dok_ext=pdf&filename=982323891.pdf| work=Dissertation, Albert-Ludwigs-Universität, Freiburg im Breisgau}}</ref><ref>{{cite journal | title=The origin of the genetic code: amino acids as cofactors in an RNA world| author=Szathmáry E| journal=Trends Genet.| year=1999| volume=15| issue=6| pages=223–9| doi=10.1016/S0168-9525(99)01730-8 | pmid = 10354582 }}</ref> 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 | author=Fiers W ''et al''| title=Complete nucleotide-sequence of bacteriophage MS2-RNA: primary and secondary structure of replicase gene| journal=Nature| year=1976| volume=260| pages=500–7| pmid=1264203 | doi = 10.1038/260500a0}}</ref> 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 | author=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=Plant Cell| year=1990| volume=2| issue=4| pages=279–89| pmid=12354959 | doi = 10.1105/tpc.2.4.279}}</ref><ref>{{cite journal |author=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 Physiol. |volume=145 |issue=4 |pages=1272–81 |year=2007 |month=December |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 | author=Ruvkun G| title=Glimpses of a tiny RNA world| journal=Science| year=2001| volume=294| issue=5543| pages=797–99| doi=10.1126/science.1066315 | pmid = 11679654}}</ref> The discovery of gene regulatory RNAs has led to attempts to develop drugs made of RNA, like [[siRNA]], to silence genes.<ref>{{cite journal | author=Fichou Y, Férec C| title=The potential of oligonucleotides for therapeutic applications| journal=Trends in Biotechnology| year=2006| volume=24| issue=12| pages=563–70| doi=10.1016/j.tibtech.2006.10.003 | pmid = 17045686}}</ref> == See also== * [[Genetics]] * [[Molecular biology]] * [[Phosphoramidite]] * [[Quantification of nucleic acids]] * [[RNA Ontology Consortium]] * [[Sequence profiling tool]] * [[RNA extraction]] * [[RNA structure|RNA structure prediction]] ==References== {{reflist|2}} ==External links== * [http://www.imb-jena.de/RNA.html RNA World website] Link collection (structures, sequences, tools, journals) * [http://ndbserver.rutgers.edu/atlas/xray/ Nucleic Acid Database] Images of DNA, RNA and complexes. {{Nucleic acids}} [[Category:RNA]] [[ar:حمض ريبي نووي]] [[bn:আরএনএ]] [[zh-min-nan:RNA]] [[bs:Ribonukleinska kiselina]] [[br:Trenkenn ribonukleek]] [[bg:РНК]] [[ca:Àcid ribonucleic]] [[cs:RNA]] [[da:RNA]] [[de:Ribonukleinsäure]] [[et:Ribonukleiinhape]] [[el:RNA]] [[es:Ácido ribonucleico]] [[eo:RNA]] [[eu:Azido erribonukleiko]] [[fo:RNA]] [[fr:Acide ribonucléique]] [[gl:Ácido ribonucleico]] [[ko:RNA]] [[hr:Ribonukleinska kiselina]] [[id:Asam ribonukleat]] [[is:Ríbósakjarnsýra]] [[it:RNA]] [[he:RNA]] [[ka:რიბონუკლეინის მჟავა]] [[la:Acidum ribonucleicum]] [[lv:Ribonukleīnskābe]] [[lb:RNS]] [[lt:Ribonukleino rūgštis]] [[hu:Ribonukleinsav]] [[mk:РНК]] [[mn:РНХ]] [[nl:RNA]] [[ja:リボ核酸]] [[no:RNA]] [[nn:Ribonukleinsyre]] [[oc:Acid ribonucleïc]] [[pl:Kwasy rybonukleinowe]] [[pt:Ácido ribonucleico]] [[ro:ARN]] [[ru:Рибонуклеиновые кислоты]] [[sq:ARN]] [[simple:RNA]] [[sk:Ribonukleová kyselina]] [[sl:Ribonukleinska kislina]] [[sr:Рибонуклеинска киселина]] [[sh:Ribonukleinska kiselina]] [[fi:RNA]] [[sv:Ribonukleinsyra]] [[ta:ரைபோ கரு அமிலம்]] [[te:రైబో కేంద్రక ఆమ్లం]] [[th:อาร์เอ็นเอ]] [[vi:RNA]] [[tr:RNA]] [[uk:РНК]] [[ur:رائبو مرکزی ترشہ]] [[yo:RNA]] [[zh:核糖核酸]]