Editing RNA (section)

== Chemical structure of RNA==
{{main|Nucleic acid structure}}

===Basic chemical composition===
[[File:Piwi-siRNA-basepairing.png|thumb|upright=1.15|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, in general, [[adenine]] (A), [[cytosine]] (C), [[guanine]] (G), or [[uracil]] (U). Adenine and guanine are [[purine]]s, and 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, making RNA a charged molecule (polyanion). The bases 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| vauthors= Barciszewski J, Frederic B, Clark C | date = 1999 | pages = 73–87 | publisher = Springer | isbn = 978-0-7923-5862-6 | oclc = 52403776 }}</ref>
or the GNRA [[tetraloop]] that has a guanine–adenine base-pair.<ref name="pmid15561141">{{cite journal |vauthors=Lee JC, Gutell RR | title = Diversity of base-pair conformations and their occurrence in rRNA structure and RNA structural motifs | journal = Journal of Molecular Biology | volume = 344 | issue = 5 | pages = 1225–49 | date = December 2004 | pmid = 15561141 | doi = 10.1016/j.jmb.2004.09.072 }}</ref>

===Differences between DNA and RNA===
[[File:50S-subunit of the ribosome 3CC2.png|thumb|Three-dimensional representation of the [[50S]] ribosomal subunit. Ribosomal RNA is in brown, proteins in blue. The active site is a small segment of rRNA, indicated in red.]]

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The chemical structure of RNA is very similar to that of [[DNA]], but differs in three primary ways:
* Unlike double-stranded DNA, RNA is usually a single-stranded molecule (ssRNA)<ref name="University of Utah-2015">{{cite web | url=https://learn.genetics.utah.edu/content/basics/rna/ | title =RNA: The Versatile Molecule | publisher =[[University of Utah]] | year =2015}}</ref> in many of its biological roles and consists of much shorter chains of nucleotides.<ref>{{cite web | url=http://www.chem.ucla.edu/harding/notes/notes_14C_nucacids.pdf | title=Nucleotides and Nucleic Acids | publisher=[[University of California, Los Angeles]] | access-date=2015-08-26 | archive-url=https://web.archive.org/web/20150923202511/http://www.chem.ucla.edu/harding/notes/notes_14C_nucacids.pdf | archive-date=2015-09-23 | url-status=dead }}</ref> However, [[RNA#Double-stranded RNA|double-stranded RNA]] (dsRNA) can form and (moreover) a single RNA molecule can, by complementary base pairing, form intrastrand double helixes, as in [[Transfer RNA|tRNA]].
* While the sugar-phosphate "backbone" of DNA contains ''[[deoxyribose]]'', RNA contains ''[[ribose]]'' instead.<ref>{{cite book | url =https://books.google.com/books?id=7-UKCgAAQBAJ&q=dna+contains+deoxyribose+rna+ribose&pg=PT386 | title =Analysis of Chromosomes | vauthors =Shukla RN | isbn =978-93-84568-17-7 | date =2014 | publisher =Agrotech Press }}{{Dead link|date=February 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Ribose has a [[Hydroxy group|hydroxyl]] group attached to the pentose ring in the [[nucleic acid nomenclature|2']] position, whereas deoxyribose does not. The hydroxyl groups in the ribose backbone make RNA more chemically [[Lability|labile]] than DNA by lowering the [[activation energy]] of [[hydrolysis]].
* The complementary base to [[adenine]] in DNA is [[thymine]], whereas in RNA, it is [[uracil]], which is an [[methylation|unmethylated]] form of thymine.<ref name=Biochemistry/>
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Like DNA, most biologically active RNAs, including [[mRNA]], [[tRNA]], [[rRNA]], [[snRNA]]s, and other [[non-coding RNA]]s, contain self-complementary sequences that allow parts of the RNA to fold<ref>{{cite journal | vauthors = Tinoco I, Bustamante C | title = How RNA folds | journal = Journal of Molecular Biology | volume = 293 | issue = 2 | pages = 271–81 | date = October 1999 | pmid = 10550208 | doi = 10.1006/jmbi.1999.3001 }}</ref> and pair with itself to form double helices. Analysis of these RNAs has revealed that they are highly structured. Unlike DNA, their structures do not consist of long double 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 | vauthors = Higgs PG | title = RNA secondary structure: physical and computational aspects | journal = Quarterly Reviews of Biophysics | volume = 33 | issue = 3 | pages = 199–253 | date = August 2000 | pmid = 11191843 | doi = 10.1017/S0033583500003620 | s2cid = 37230785 }}</ref> For instance, determination of the structure of the ribosome—an [[Ribonucleoprotein|RNA-protein complex]] that catalyzes the assembly of proteins—revealed that its active site is composed entirely of RNA.<ref name=ribosome_activity>{{cite journal | vauthors = Nissen P, Hansen J, Ban N, Moore PB, Steitz TA | title = The structural basis of ribosome activity in peptide bond synthesis | journal = Science | volume = 289 | issue = 5481 | pages = 920–30 | date = August 2000 | pmid = 10937990 | doi = 10.1126/science.289.5481.920 | bibcode = 2000Sci...289..920N }}</ref>

[[File:RNA chemical structure.GIF|class=skin-invert-image|thumb|left|Structure of a fragment of an RNA, showing a guanosyl subunit]]
An important structural component of RNA that distinguishes it from DNA is the presence of a [[hydroxyl]] group at the 2' position of the [[Ribose|ribose sugar]]. The presence of this functional group causes the helix to mostly take the [[A-DNA|A-form geometry]],<ref>{{cite journal |vauthors=Salazar M, Fedoroff OY, Miller JM, Ribeiro NS, Reid BR | title = The DNA strand in DNA.RNA hybrid duplexes is neither B-form nor A-form in solution | journal = Biochemistry | volume = 32 | issue = 16 | pages = 4207–15 | date = April 1993 | pmid = 7682844 | doi = 10.1021/bi00067a007 }}</ref> although in single strand dinucleotide contexts, RNA can rarely also adopt the B-form most commonly observed in DNA.<ref>{{cite journal | vauthors = Sedova A, Banavali NK | title = RNA approaches the B-form in stacked single strand dinucleotide contexts | journal = Biopolymers | volume = 105 | issue = 2 | pages = 65–82 | date = February 2016 | pmid = 26443416 | doi = 10.1002/bip.22750 | s2cid = 35949700 }}</ref>  The A-form geometry results in a very deep and narrow major groove and a shallow and wide minor groove.<ref>{{cite journal | vauthors = Hermann T, Patel DJ | title = RNA bulges as architectural and recognition motifs | journal = Structure | volume = 8 | issue = 3 | pages = R47–54 | date = March 2000 | pmid = 10745015 | doi = 10.1016/S0969-2126(00)00110-6 | doi-access = free }}</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 | vauthors = Mikkola S, Stenman E, 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=Journal of the Chemical Society, Perkin Transactions 2|date=1999|pages=1619–26|doi=10.1039/a903691a|issue=8}}</ref>

===Secondary and tertiary structures===
The functional form of single-stranded RNA molecules, just like proteins, frequently requires a specific spatial [[RNA Tertiary Structure|tertiary structure]]. The scaffold for this structure is provided by [[secondary structure|secondary structural]] elements that are hydrogen bonds within the molecule. This leads to several recognizable "domains" of secondary structure like [[hairpin loop]]s, bulges, and [[internal loop]]s.<ref>{{cite journal | vauthors = 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 = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 19 | pages = 7287–92 | date = May 2004 | pmid = 15123812 | pmc = 409911 | doi = 10.1073/pnas.0401799101 | bibcode = 2004PNAS..101.7287M | doi-access = free }}</ref> In order to create, i.e., design, RNA for any given secondary structure, two or three bases would not be enough, but four bases are enough.<ref>{{cite journal | vauthors = Burghardt B, Hartmann AK |
title = RNA secondary structure design | journal = Physical Review E | volume = 75 | issue = 2 | pages = 021920 | date = February 2007 | doi = 10.1103/PhysRevE.75.021920 |
pmid = 17358380 | url = https://link.aps.org/doi/10.1103/PhysRevE.75.021920| arxiv = physics/0609135 |
bibcode = 2007PhRvE..75b1920B |
s2cid = 17574854 }}</ref> This is likely why nature has "chosen" a four base alphabet: fewer than four would not allow the creation of all structures, while more than four bases are not necessary to do so. Since RNA is charged, metal ions such as [[Magnesium|Mg<sup>2+</sup>]] are needed to stabilise many secondary and [[RNA Tertiary Structure|tertiary structures]].<ref>{{cite journal | vauthors = Tan ZJ, Chen SJ | title = Salt dependence of nucleic acid hairpin stability | journal = Biophysical Journal | volume = 95 | issue = 2 | pages = 738–52 | date = July 2008 | pmid = 18424500 | pmc = 2440479 | doi = 10.1529/biophysj.108.131524 | bibcode = 2008BpJ....95..738T }}</ref>

The naturally occurring [[enantiomer]] of RNA is <small>D</small>-RNA composed of <small>D</small>-ribonucleotides. All chirality centers are located in the <small>D</small>-ribose. By the use of <small>L</small>-ribose or rather <small>L</small>-ribonucleotides, <small>L</small>-RNA can be synthesized. <small>L</small>-RNA is much more stable against degradation by [[ribonuclease|RNase]].<ref name="pmid25236655">{{cite journal | vauthors = Vater A, Klussmann S | title = Turning mirror-image oligonucleotides into drugs: the evolution of Spiegelmer(®) therapeutics | journal = Drug Discovery Today | volume = 20 | issue = 1 | pages = 147–55 | date = January 2015 | pmid = 25236655 | doi = 10.1016/j.drudis.2014.09.004 | doi-access = free }}</ref>

Like other structured [[biopolymer]]s such as proteins, one can define topology of a folded RNA molecule. This is often done based on arrangement of intra-chain contacts within a folded RNA, termed as [[circuit topology]].

===Chemical modifications===
[[File:Ciliate telomerase RNA.JPG|class=skin-invert-image|thumb|upright=1.25|[[Secondary structure]] of a [[telomerase RNA]]]]
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|vauthors=Jankowski JA, Polak JM|date=1996|page=[https://archive.org/details/clinicalgeneanal0000unse/page/14 14]|publisher=Cambridge University Press|isbn=978-0-521-47896-0|oclc=33838261|url=https://archive.org/details/clinicalgeneanal0000unse/page/14}}</ref> but these bases and attached sugars can be modified in numerous ways as the RNAs mature. [[Pseudouridine]] (Ψ), in which the linkage between uracil and ribose is changed from a C–N bond to a C–C bond, and [[5-methyluridine|ribothymidine]] (T) are found in various places (the most notable ones being in the TΨC loop of [[tRNA]]).<ref>{{cite journal | vauthors = Yu Q, Morrow CD | title = Identification of critical elements in the tRNA acceptor stem and T(Psi)C loop necessary for human immunodeficiency virus type 1 infectivity | journal = Journal of Virology | volume = 75 | issue = 10 | pages = 4902–6 | date = May 2001 | pmid = 11312362 | pmc = 114245 | doi = 10.1128/JVI.75.10.4902-4906.2001 }}</ref> Another notable modified base is [[hypoxanthine]], a deaminated adenine base whose [[nucleoside]] is called [[inosine]] (I). Inosine plays a key role in the [[wobble hypothesis]] of the [[genetic code]].<ref>{{cite journal | vauthors = Elliott MS, Trewyn RW | title = Inosine biosynthesis in transfer RNA by an enzymatic insertion of hypoxanthine | journal = The Journal of Biological Chemistry | volume = 259 | issue = 4 | pages = 2407–10 | date = February 1984 | doi = 10.1016/S0021-9258(17)43367-9 | pmid = 6365911 | doi-access = free }}</ref>

There are more than 100 other naturally occurring modified nucleosides.<ref>{{cite journal | vauthors = Cantara WA, Crain PF, Rozenski J, McCloskey JA, Harris KA, Zhang X, Vendeix FA, Fabris D, Agris PF | title = The RNA Modification Database, RNAMDB: 2011 update | journal = Nucleic Acids Research | volume = 39 | issue = Database issue | pages = D195-201 | date = January 2011 | pmid = 21071406 | pmc = 3013656 | doi = 10.1093/nar/gkq1028 }}</ref> The greatest structural diversity of modifications can be found in [[tRNA]],<ref>{{cite book|title=TRNA: Structure, biosynthesis, and function| vauthors = Söll D, RajBhandary U |date=1995|page=165|publisher=ASM Press|isbn=978-1-55581-073-3|oclc=183036381 }}</ref> while pseudouridine and nucleosides with [[2'-O-methylation|2'-O-methylribose]] often present in rRNA are the most common.<ref>{{cite journal | vauthors = Kiss T | title = Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs | journal = The EMBO Journal | volume = 20 | issue = 14 | pages = 3617–22 | date = July 2001 | pmid = 11447102 | pmc = 125535 | doi = 10.1093/emboj/20.14.3617 }}</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<ref>{{cite journal | vauthors = Tirumalai MR, Rivas M, Tran Q, Fox GE | title = The Peptidyl Transferase Center: a Window to the Past. | journal = Microbiol Mol Biol Rev | volume = 85 | issue = 4 | pages = e0010421 | date = November 2021 | pmid = 34756086 | doi = 10.1128/MMBR.00104-21 | pmc = 8579967 | bibcode = 2021MMBR...85...21T }}</ref> and the subunit interface, implying that they are important for normal function.<ref>{{cite journal | vauthors = 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 | volume = 11 | issue = 2 | pages = 425–35 | date = February 2003 | pmid = 12620230 | doi = 10.1016/S1097-2765(03)00040-6 | doi-access = free }}</ref>