Editing Exon

{{Short description|Region of a transcribed gene present in the final functional mRNA molecule}}
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{{Other uses}}
{{distinguish|Axon|Exxon|Hexon|Nexon}}
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[[File:RNA splicing diagram en.svg|thumb|Introns are removed and exons joined in the process of RNA splicing. RNAs could be [[mRNA]] or [[non-coding RNA]].]]
An '''exon''' is any part of a [[gene]] that will form a part of the final mature [[RNA]] produced by that gene after [[intron]]s have been removed by [[RNA splicing]]. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence in RNA transcripts. In RNA splicing, introns are removed and exons are covalently joined to one another as part of generating the mature [[RNA]]. Just as the entire set of genes for a [[species]] constitutes the [[genome]], the entire set of exons constitutes the [[exome]].

==History==
The term ''exon'' is a shortening of the phrase ''expressed region'' and was coined by American [[biochemist]] [[Walter Gilbert]] in 1978: "The notion of the [[cistron]]... must be replaced by that of a transcription unit containing regions which will be lost from the mature messenger{{spaced ndash}}which I suggest we call introns (for intragenic regions){{spaced ndash}}alternating with regions which will be expressed{{spaced ndash}}exons."<ref>{{cite journal |author=Gilbert W |title=Why genes in pieces? |journal=Nature |volume=271 |issue=5645 |pages=501 |date=February 1978 |pmid=622185 |doi=10.1038/271501a0|bibcode=1978Natur.271..501G |doi-access=free }}</ref>

This definition was originally made for protein-coding transcripts that are spliced before being translated.  The term later came to include sequences removed from [[rRNA]]<ref>{{cite journal |vauthors=Kister KP, Eckert WA |title=Characterization of an authentic intermediate in the self-splicing process of ribosomal precursor RNA in macronuclei of Tetrahymena thermophila |journal=Nucleic Acids Research |volume=15 |issue=5 |pages=1905–20 |date=March 1987 |pmid=3645543 |pmc=340607 |doi=10.1093/nar/15.5.1905}}</ref> and [[tRNA]],<ref>{{cite journal |vauthors=Valenzuela P, Venegas A, Weinberg F, Bishop R, Rutter WJ|title=Structure of yeast phenylalanine-tRNA genes: an intervening DNA segment within the region coding for the tRNA |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=75 |issue=1 |pages=190–4 |date=January 1978 |pmid=343104 |pmc=411211 |doi=10.1073/pnas.75.1.190|bibcode=1978PNAS...75..190V |doi-access=free }}</ref> and other [[ncRNA]]<ref>{{cite journal |last1=Khan |first1=MR |last2=Wellinger |first2=RJ |last3=Laurent |first3=B |title=Exploring the Alternative Splicing of Long Noncoding RNAs. |journal=Trends in Genetics |date=August 2021 |volume=37 |issue=8 |pages=695–698 |doi=10.1016/j.tig.2021.03.010 |pmid=33892960|s2cid=233382870 }}</ref> and it also was used later for RNA molecules originating from different parts of the genome that are then [[ligation (molecular biology)|ligated]] by trans-splicing.<ref>{{cite journal |vauthors=Liu AY, Van der Ploeg LH, Rijsewijk FA, Borst P |title=The transposition unit of variant surface glycoprotein gene 118 of Trypanosoma brucei. Presence of repeated elements at its border and absence of promoter-associated sequences |journal=Journal of Molecular Biology |volume=167 |issue=1 |pages=57–75 |date=June 1983 |pmid=6306255 |doi=10.1016/S0022-2836(83)80034-5}}</ref>

== Contribution to genomes and size distribution ==
Although unicellular [[eukaryote]]s such as yeast have either no introns or very few, [[Animal|metazoans]] and especially [[vertebrate]] genomes have a large fraction of [[Noncoding DNA|non-coding DNA]]. For instance, in the [[human genome]] only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being [[Intergenic region|intergenic DNA]].<ref>{{cite journal | author = Venter J.C.|author-link= Craig Venter| year = 2000 | title = The Sequence of the Human Genome | journal = Science | volume = 291 | issue = 5507| pages = 1304–51 | doi=10.1126/science.1058040 | pmid=11181995| bibcode = 2001Sci...291.1304V |display-authors=etal| doi-access = free }}</ref> This can provide a practical advantage in [[omics]]-aided [[health care]] (such as [[precision medicine]]) because it makes commercialized [[exome sequencing|whole exome sequencing]] a smaller and less expensive challenge than commercialized [[whole genome sequencing]]. The large variation in [[genome size]] and [[C-value]] across [[Organism|life forms]] has posed an interesting challenge called the [[C-value#Variation among species|C-value enigma]].

Across all eukaryotic genes in GenBank, there were (in 2002), on average, 5.48 exons per protein coding gene. The average exon encoded 30-36 [[amino acid]]s.<ref name="pmid11752290">{{cite journal |vauthors=Sakharkar M, Passetti F, de Souza JE, Long M, de Souza SJ |title=ExInt: an Exon Intron Database |journal=Nucleic Acids Res. |volume=30 |issue=1 |pages=191–4 |year=2002 |pmid=11752290 |pmc=99089 |doi= 10.1093/nar/30.1.191}}</ref> While the longest exon in the human genome is 11555 [[Base pair|bp]] long, several exons have been found to be only 2 bp long.<ref>{{cite journal|author1=Sakharkar M.K.|author2=Chow VT|author3=Kangueane P.|year=2004|pmid=15217358|journal=In Silico Biol|volume=4|issue=4|pages=387–93|title=Distributions of exons and introns in the human genome}}</ref> A single-nucleotide exon has been reported from the ''[[Arabidopsis thaliana|Arabidopsis]]'' genome.<ref>{{cite journal | author = Guo Lei, Liu Chun-Ming | year = 2015 | title = ''A single-nucleotide exon found in ''Arabidopsis | journal = Scientific Reports | volume = 5 | page = 18087 | doi = 10.1038/srep18087 | pmid = 26657562 | pmc = 4674806 | bibcode = 2015NatSR...518087G }}</ref> In humans, like protein coding [[mRNA]], most [[non-coding RNA]] also contain multiple exons<ref>{{cite journal |last1=Derrien |first1=T |last2=Johnson |first2=R |last3=Bussotti |first3=G |last4=Tanzer |first4=A |last5=Djebali |first5=S |last6=Tilgner |first6=H |last7=Guernec |first7=G |last8=Martin |first8=D |last9=Merkel |first9=A |last10=Knowles |first10=DG |last11=Lagarde |first11=J |last12=Veeravalli |first12=L |last13=Ruan |first13=X |last14=Ruan |first14=Y |last15=Lassmann |first15=T |last16=Carninci |first16=P |last17=Brown |first17=JB |last18=Lipovich |first18=L |last19=Gonzalez |first19=JM |last20=Thomas |first20=M |last21=Davis |first21=CA |last22=Shiekhattar |first22=R |last23=Gingeras |first23=TR |last24=Hubbard |first24=TJ |last25=Notredame |first25=C |last26=Harrow |first26=J |last27=Guigó |first27=R |title=The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. |journal=Genome Research |date=September 2012 |volume=22 |issue=9 |pages=1775–89 |doi=10.1101/gr.132159.111 |pmid=22955988|pmc=3431493 }}</ref>

==Structure and function==
[[File:Gene structure.svg|frame|right|Exons in a messenger RNA precursor (pre-mRNA). Exons can include both sequences that code for amino acids (red) and untranslated sequences (grey). Introns — those parts of the pre-mRNA that are not in the mRNA — (blue) are removed, and the exons are joined (spliced) to form the final functional mRNA. The 5′ and 3′ ends of the mRNA are marked to differentiate the two untranslated regions (grey).]]

In protein-coding genes, the exons include both the protein-coding sequence and the 5′- and 3′-[[untranslated region]]s (UTR). Often the first exon includes both the 5′-UTR and the first part of the coding sequence, but exons containing only regions of 5′-UTR or (more rarely) 3′-UTR occur in some genes, i.e. the UTRs may contain introns.<ref>{{cite journal|last1=Bicknell|first1=AA|s2cid=5808466|title=Introns in UTRs: Why we should stop ignoring them.|journal=BioEssays|date=December 2012|volume=34|issue=12|pages=1025–1034|doi=10.1002/bies.201200073|pmid=23108796|doi-access=free}}</ref> Some  [[non-coding RNA]] transcripts also have exons and introns.

Mature mRNAs originating from the same gene need not include the same exons, since different introns in the pre-mRNA can be removed by the process of [[alternative splicing]].

Exonization is the creation of a new exon, as a result of mutations in [[introns]].<ref>{{cite journal |author=Sorek R |title=The birth of new exons: mechanisms and evolutionary consequences |journal=RNA |volume=13 |issue=10 |pages=1603–8 |date=October 2007 |pmid=17709368 |pmc=1986822 |doi=10.1261/rna.682507}}</ref>

==Experimental approaches using exons==
[[Exon trapping]] or '[[gene trapping]]' is a [[molecular biology]] technique that exploits the existence of the intron-exon [[RNA splicing|splicing]] to find new genes.<ref>{{cite journal |author1=Duyk G. M |author2=Kim S. W. |author3=Myers R. M |author4=Cox D. R | year = 1990 | title = Exon Trapping: a Genetic Screen to Identify Candidate Transcribed Sequences in Cloned Mammalian Genomic DNA | journal = Proceedings of the National Academy of Sciences | volume = 87 | issue = 22| pages = 8995–8999 | doi=10.1073/pnas.87.22.8995|pmid=2247475 |pmc=55087 |bibcode=1990PNAS...87.8995D |doi-access=free }}</ref> The first exon of a 'trapped' gene splices into the exon that is contained in the [[insertional DNA]]. This new exon contains the ORF for a [[reporter gene]] that can now be expressed using the [[Enhancer (genetics)|enhancer]]s that control the target gene. A scientist knows that a new gene has been trapped when the reporter gene is expressed.

Splicing can be experimentally modified so that targeted exons are excluded from mature mRNA transcripts by blocking the access of splice-directing small nuclear ribonucleoprotein particles (snRNPs) to pre-mRNA using [[Morpholino|Morpholino antisense oligos]].<ref>{{cite journal |author=Morcos PA |title=Achieving targeted and quantifiable alteration of mRNA splicing with Morpholino oligos |journal=Biochemical and Biophysical Research Communications |volume=358 |issue=2 |pages=521–7 |date=June 2007 |pmid=17493584 |doi=10.1016/j.bbrc.2007.04.172}}</ref> This has become a standard technique in [[developmental biology]].  Morpholino oligos can also be targeted to prevent molecules that regulate splicing (e.g. splice enhancers, splice suppressors) from binding to pre-mRNA, altering patterns of splicing.

==Common misuse of the term==

Common incorrect uses of the term ''exon'' are that 'exons code for protein', or 'exons code for amino-acids' or 'exons are translated'. However, these sorts of definitions only cover [[Protein coding gene|protein-coding genes]], and omit those exons that become part of a [[non-coding RNA]]<ref>{{cite journal |last1=Khan |first1=MR |last2=Wellinger |first2=RJ |last3=Laurent |first3=B |title=Exploring the Alternative Splicing of Long Noncoding RNAs. |journal=Trends in Genetics |date=August 2021 |volume=37 |issue=8 |pages=695–698 |doi=10.1016/j.tig.2021.03.010 |pmid=33892960|s2cid=233382870 }}</ref> or the [[untranslated region]] of an [[mRNA]].<ref>{{cite journal |last1=Lu |first1=J |last2=Williams |first2=JA |last3=Luke |first3=J |last4=Zhang |first4=F |last5=Chu |first5=K |last6=Kay |first6=MA |title=A 5' Noncoding Exon Containing Engineered Intron Enhances Transgene Expression from Recombinant AAV Vectors in vivo. |journal=Human Gene Therapy |date=January 2017 |volume=28 |issue=1 |pages=125–134 |doi=10.1089/hum.2016.140 |pmid=27903072|pmc=5278795 }}</ref><ref>{{cite journal |last1=Chung |first1=BY |last2=Simons |first2=C |last3=Firth |first3=AE |last4=Brown |first4=CM |last5=Hellens |first5=RP |title=Effect of 5'UTR introns on gene expression in Arabidopsis thaliana. |journal=BMC Genomics |date=19 May 2006 |volume=7 |pages=120 |doi=10.1186/1471-2164-7-120 |pmid=16712733|pmc=1482700 |doi-access=free }}</ref> Such incorrect definitions still occur in overall reputable secondary sources.<ref>{{Cite web |title=Exon |url=https://www.genome.gov/genetics-glossary/Exon |archive-url=https://web.archive.org/web/20230316084632/https://www.genome.gov/genetics-glossary/Exon |archive-date=2023-03-16 |access-date=2023-03-23 |website=Genome.gov |language=en}}</ref><ref>{{Cite web |title=Exon |url=https://www.nature.com/scitable/definition/exon-exons-270/ |archive-url=https://web.archive.org/web/20230323060403/https://www.nature.com/scitable/definition/exon-exons-270/ |archive-date=2023-03-23 |access-date=2023-03-23 |website=www.nature.com |publisher=Scitable |language=en}}</ref>

==See also==
* [[DBASS3/5]]
* [[Exitron]]
* [[Exon-intron database]]
* [[Exon shuffling]]
* [[Interrupted gene]]
* [[Outron]]
* [[Twintron]]
* [[Untranslated region]] (UTR)
* [[Poison exon]]

==References==
{{Reflist}}

===Bibliography===
*{{cite journal |author=Zhang MQ |title=Statistical features of human exons and their flanking regions |journal=Human Molecular Genetics |volume=7 |issue=5 |pages=919–32 |date=May 1998  |pmid=9536098 |doi=10.1093/hmg/7.5.919|doi-access=free }}
*{{cite journal |vauthors=Thanaraj TA, Robinson AJ |title=Prediction of exact boundaries of exons |journal=Brief. Bioinform. |volume=1 |issue=4 |pages=343–56 |date=November 2000|pmid=11465052 |doi=10.1093/bib/1.4.343|doi-access=free }}

==External links==
{{wiktionary|exon}}
* [http://wormweb.org/exonintron Exon-intron graphic maker]

{{Post transcriptional modification}}
{{Authority control}}

[[Category:DNA]]
[[Category:Spliceosome]]
[[Category:RNA splicing]]