Editing Inverted repeat (section)

==Biological features and functionality==
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===Origin of inverted repeats===
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===Conditions that favor synthesis===
The diverse genome-wide repeats are derived from [[transposable element]]s, which are now understood to "jump" about different genomic locations, without transferring their original copies.<ref name=Watson>{{cite book|last=School|first=James D. Watson, Cold Spring Harbor Laboratory, Tania A. Baker, Massachusetts Institute of Technology, Stephen P. Bell, Massachusetts Institute of Technology, Alexander Gann, Cold Spring Harbor Laboratory, Michael Levine, University of California, Berkeley, Richard Losik, Harvard University; with Stephen C. Harrison, Harvard Medical|title=Molecular biology of the gene|publisher=Benjamin-Cummings Publishing Company|location=Boston|isbn=9780321762436|edition=Seventh|year=2014}}</ref> Subsequent shuttling of the same sequences over numerous generations ensures their multiplicity throughout the genome.<ref name=Watson /> The limited [[Genetic recombination|recombination]] of the sequences between two distinct sequence elements known as [[Site-specific recombination|conservative site-specific recombination]] (CSSR) results in inversions of the DNA segment, based on the arrangement of the recombination recognition sequences on the donor DNA and recipient DNA.<ref name=Watson /> Again, the orientation of two of the recombining sites within the donor DNA molecule relative to the asymmetry of the intervening DNA cleavage sequences, known as the crossover region, is pivotal to the formation of either inverted repeats or direct repeats.<ref name=Watson /> Thus, recombination occurring at a pair of inverted sites will invert the DNA sequence between the two sites.<ref name=Watson /> <!--Very stable chromosomes have been observed with a comparatively fewer number of inverted repeats than direct repeats, suggesting a relationship between the stability of and the number of  repeats.-->Very stable chromosomes have been observed with comparatively fewer numbers of inverted repeats than direct repeats, suggesting a relationship between chromosome stability and the number of repeats.<ref name=Achaz>{{cite journal|last=Achaz|first=G|author2=Coissac, E |author3=Netter, P |author4= Rocha, EP |title=Associations between inverted repeats and the structural evolution of bacterial genomes|journal=Genetics|date=August 2003|volume=164|issue=4|pages=1279–89|doi=10.1093/genetics/164.4.1279|pmid=12930739|pmc=1462642}}</ref>
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===Most common biological functions using Inverted Repeats===
:This section is "under construction" and will be completed by mid-December.
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===Regions where presence is obligatory===
Terminal inverted repeats have been observed in the DNA of various eukaryotic transposons, even though their source remains unknown.<ref name=Zhang>{{cite journal|last=Zhang|first=HH|author2=Xu, HE |author3=Shen, YH |author4=Han, MJ |author5= Zhang, Z |title=The Origin and Evolution of Six Miniature Inverted-Repeat Transposable Elements in Bombyx mori and Rhodnius prolixus|journal=Genome Biology and Evolution|date=January 2013|volume=5|issue=11|pages=2020–31|pmid=24115603|doi=10.1093/gbe/evt153 |pmc=3845634}}</ref> Inverted repeats are principally found at the origins of replication of cell organism and organelles that range from phage plasmids, mitochondria, and eukaryotic viruses to mammalian cells.<ref name=Pearson>{{cite journal|last=Pearson|first=CE|author2=Zorbas, H |author3=Price, GB |author4= Zannis-Hadjopoulos, M |s2cid=22204780|title=Inverted repeats, stem-loops, and cruciforms: significance for initiation of DNA replication|journal=Journal of Cellular Biochemistry|date=October 1996|volume=63|issue=1|pages=1–22|pmid=8891900|doi=10.1002/(SICI)1097-4644(199610)63:1<1::AID-JCB1>3.0.CO;2-3}}</ref> The replication origins of the phage G4 and other related phages comprise a segment of nearly 139 nucleotide bases that include three inverted repeats that are essential for replication priming.<ref name=Pearson />

===In the genome===
To a large extent, portions of nucleotide repeats are quite often observed as part of rare DNA combinations.<ref name=Heringa /> The three main repeats which are largely found in particular DNA constructs include the closely precise homopurine-homopyrimidine inverted repeats, which is otherwise referred to as H palindromes, a common occurrence in triple helical H conformations that may comprise either the TAT or CGC nucleotide triads. The others could be described as long inverted repeats having the tendency to produce hairpins and cruciform, and finally direct tandem repeats, which commonly exist in structures described as slipped-loop, cruciform and left-handed Z-DNA.<ref name=Heringa />

===Common in different organisms===
Past studies suggest that repeats are a common feature of [[eukaryotes]] unlike the [[prokaryotes]] and [[archaea]].<ref name=Heringa>{{cite journal|last=Heringa|first=J|title=Detection of internal repeats: how common are they?|journal=Current Opinion in Structural Biology|date=June 1998|volume=8|issue=3|pages=338–45|pmid=9666330|doi=10.1016/S0959-440X(98)80068-7}}</ref> Other reports suggest that irrespective of the comparative shortage of repeat elements in prokaryotic genomes, they nevertheless contain hundreds or even thousands of large repeats.<ref>{{cite journal|last=Treangen|first=TJ|author2=Abraham, AL |author3=Touchon, M |author4= Rocha, EP |title=Genesis, effects and fates of repeats in prokaryotic genomes|journal=FEMS Microbiology Reviews|date=May 2009|volume=33|issue=3|pages=539–71|pmid=19396957|doi=10.1111/j.1574-6976.2009.00169.x|url=https://academic.oup.com/femsre/article-pdf/33/3/539/18141891/33-3-539.pdf|doi-access=free}}</ref>   Current genomic analysis seem to suggest the existence of a large excess of perfect inverted repeats in many prokaryotic genomes as compared to eukaryotic genomes.<ref name=Ladoukakis>{{cite journal|last=Ladoukakis|first=ED|author2=Eyre-Walker, A|title=The excess of small inverted repeats in prokaryotes|journal=Journal of Molecular Evolution|date=September 2008|volume=67|issue=3|pages=291–300|pmid=18696026|doi=10.1007/s00239-008-9151-z|url=http://www.lifesci.susx.ac.uk/home/Adam_Eyre-Walker/Website/Publications_files/LadoukakisJME08.pdf|bibcode=2008JMolE..67..291L|citeseerx=10.1.1.578.7466|s2cid=29953202}}</ref>

[[File:Pseudoknot-Inverted-Repeats.gif|thumb|500 px| Pseudoknot with four sets of inverted repeats. Inverted repeats 1 and 2 create the stem for stem-loop A and are part of the loop for stem-loop B. Similarly, inverted repeats 3 and 4 form the stem for stem-loop B and are part of the loop for stem-loop A.]]

For quantification and comparison of inverted repeats between several species, namely on archaea, see <ref>{{cite book|last=Hosseini|first=M|author2=Pratas, D |author3=Pinho, AJ |title= 11th International Conference on Practical Applications of Computational Biology & Bioinformatics|chapter=On the Role of Inverted Repeats in DNA Sequence Similarity|series=Advances in Intelligent Systems and Computing|publisher=Springer|volume=616|pages=228–236|date=2017|doi=10.1007/978-3-319-60816-7_28|isbn=978-3-319-60815-0}}</ref>

===Inverted repeats in pseudoknots===
[[Pseudoknot]]s are common structural motifs found in RNA.  They are formed by two nested [[stem-loop]]s such that the stem of one structure is formed from the loop of the other.  There are multiple folding [[topology|topologies]] among pseudoknots and great variation in loop lengths, making them a structurally diverse group.<ref name=Staple>{{cite journal|last=Staple|first=DW|author2=Butcher, SE|title=Pseudoknots: RNA structures with diverse functions.|journal=PLOS Biology|date=June 2005|volume=3|issue=6|pages=e213|pmid=15941360|doi=10.1371/journal.pbio.0030213|pmc=1149493 |doi-access=free }} {{open access}}</ref>

Inverted repeats are a key component of pseudoknots as can be seen in the illustration of a naturally occurring pseudoknot found in the human [[telomerase RNA component]].<ref name=chen-greider>{{cite journal|last=Chen|first=JL|author2=Greider, CW|title=Functional analysis of the pseudoknot structure in human telomerase RNA.|journal=Proceedings of the National Academy of Sciences of the United States of America|date=Jun 7, 2005|volume=102|issue=23|pages=8080–5; discussion 8077–9|pmid=15849264|doi=10.1073/pnas.0502259102|pmc=1149427|bibcode=2005PNAS..102.8080C|doi-access=free}}</ref> Four different sets of inverted repeats are involved in this structure.  Sets 1 and 2 are the stem of stem-loop A and are part of the loop for stem-loop B.  Similarly, sets 3 and 4 are the stem for stem-loop B and are part of the loop for stem-loop A.

Pseudoknots play a number of different roles in biology.  The telomerase pseudoknot in the illustration is critical to that enzyme's activity.<ref name=chen-greider />  The [[ribozyme]] for the [[Hepatitis D|''hepatitis delta virus (HDV)'']] folds into a double-pseudoknot structure and self-cleaves its circular genome to produce a single-genome-length RNA.  Pseudoknots also play a role in programmed [[ribosomal frameshift]]ing found in some viruses and required in the replication of [[retroviruses]].<ref name=Staple />{{Clear}}

===In riboswitches===
Inverted repeats play an important role in [[riboswitch]]es, which are RNA regulatory elements that control the expression of genes that produce the mRNA, of which they are part.<ref name="Watson"/>  A simplified example of the [[flavin mononucleotide]] (FMN) riboswitch is shown in the illustration. This riboswitch exists in the [[mRNA]] transcript and has several [[stem-loop]] structures upstream from the [[coding region]].  However, only the key stem-loops are shown in the illustration, which has been greatly simplified to help show the role of the inverted repeats.  There are multiple inverted repeats in this riboswitch as indicated in green (yellow background) and blue (orange background). [[File:Ribo100r.gif|thumb|800 px|left]]
{{Clear}}
In the absence of FMN, the Anti-termination structure is the preferred [[Conformation activity relationship|conformation]] for the mRNA transcript. It is created by base-pairing of the inverted repeat region circled in red.  When FMN is present, it may bind to the loop and prevent formation of the Anti-termination structure.  This allows two different sets of inverted repeats to base-pair and form the Termination structure.<ref>{{cite journal|last=Winkler|first=WC|author2=Cohen-Chalamish, S |author3=Breaker, RR |title=An mRNA structure that controls gene expression by binding FMN.|journal=Proceedings of the National Academy of Sciences of the United States of America|date=Dec 10, 2002|volume=99|issue=25|pages=15908–13|pmid=12456892|doi=10.1073/pnas.212628899|pmc=138538|bibcode=2002PNAS...9915908W|doi-access=free}}</ref>  The stem-loop on the 3' end is a [[Terminator (genetics)|transcriptional terminator]] because the sequence immediately following it is a string of uracils (U).  If this stem-loop forms (due to the presence of FMN) as the growing RNA strand emerges from the [[RNA polymerase]] complex, it will create enough structural tension to cause the RNA strand to dissociate and thus terminate transcription.  The dissociation occurs easily because the base-pairing between the U's in the RNA and the A's in the template strand are the weakest of all base-pairings.<ref name=Watson />  Thus, at higher concentration levels, FMN down-regulates its own transcription by increasing the formation of the termination structure.