View source for Biology:Intron-mediated enhancement

'''Intron-mediated enhancement''' (IME) is the ability of an [[Biology:Intron|intron]] sequence to enhance the [[Biology:Gene expression|expression]] of a [[Biology:Gene|gene]] containing that intron. In particular, the intron must be present in the transcribed region of the gene for enhancement to occur, differentiating IME from the action of typical [[Biology:Transcription factor|transcriptional enhancers]].<ref>{{Cite journal|title = Intron-mediated regulation of gene expression|journal = Current Topics in Microbiology and Immunology|date = 2008-01-01|issn = 0070-217X|pmid = 18630758|pages = 277–290|volume = 326|first = A. B.|last = Rose|doi = 10.1007/978-3-540-76776-3_15|isbn = 978-3-540-76775-6}}</ref> Descriptions of this phenomenon were first published in cultured [[Biology:Maize|maize]] cells in 1987,<ref>{{Cite journal|title = Introns increase gene expression in cultured maize cells|journal = Genes & Development|date = 1987-12-01|issn = 0890-9369|pmid = 2828168|pages = 1183–1200|volume = 1|issue = 10|first1 = J.|last1 = Callis|first2 = M.|last2 = Fromm|first3 = V.|last3 = Walbot|doi=10.1101/gad.1.10.1183|doi-access = free}}</ref> and the term "intron-mediated enhancement" was subsequently coined in 1990.<ref>{{cite journal 
|last1=Mascarenhas
|first1=D
|last2=Mettler
|first2=IJ
|last3=Pierce
|first3=DA
|last4=Lowe
|first4=HW
|year=1990 
|title=Intron-mediated enhancement of heterologous gene expression in maize
|journal=[[Biology:Plant Molecular Biology|Plant Molecular Biology]] 
|volume=15 
|issue=6
|pages=913–920
|quote=no 
|doi=10.1007/BF00039430
|pmid=2103480|s2cid=28769100
}}</ref> A number of publications have demonstrated that this phenomenon is conserved across [[Biology:Eukaryote|eukaryote]]s, including humans,<ref>{{cite journal 
|last1=Jonsson
|first1=JJ
|last2=Foresman
|first2=MD
|last3=Wilson
|first3=N
|last4=McIvor
|first4=RS
|year=1990 
|pmid=1620616
|title=Intron requirement for expression of the human purine nucleoside phosphorylase gene
|journal=[[Chemistry:Nucleic Acids Research|Nucleic Acids Research]] 
|pmc=312458 
|volume=20
|issue=12
|pages=3191–3198
|doi=10.1093/nar/20.12.3191}}</ref> mice,<ref>{{cite journal 
|last1=Palmiter
|first1=RD
|last2=Sandgren
|first2=EP
|last3=Avarbock
|first3=MR
|last4=Allen
|first4=DD
|last5=Brinster
|first5=RL
|year=1991 
|pmid=1988947
|pmc=50834
|title=Heterologous introns can enhance expression of transgenes in mice
|journal=PNAS 
|volume=88
|issue=2
|pages=478–482
|quote=no 
|doi=10.1073/pnas.88.2.478|bibcode=1991PNAS...88..478P
|doi-access=free
}}</ref> ''[[Biology:Arabidopsis thaliana|Arabidopsis]]'',<ref>{{cite journal 
|last1=Rose
|first1=AB
|last2=Last
|first2=RL
|year=2003
|title=Introns act post-transcriptionally to increase expression of the Arabidopsis thaliana tryptophan pathway gene PAT1
|journal=The Plant Journal
|volume=11
|issue=3
|pages=455–464
|doi=10.1046/j.1365-313X.1997.11030455.x 
|pmid=9107035|doi-access=
}}</ref> rice,<ref>{{cite journal 
|last1=Jeon
|first1=JS
|last2=Lee
|first2=S
|last3=Jung
|first3=KH
|last4=Jun
|first4=SH
|last5=Kim
|first5=C
|last6=An
|first6=G
|year=2000
|title=Tissue-Preferential Expression of a Rice α-Tubulin Gene, OsTubA1, Mediated by the First Intron
|journal=Plant Physiology
|volume=123
|issue=3
|pages=1005–1014
|doi=10.1104/pp.123.3.1005 
|pmid=10889249 
|pmc=59063}}</ref><ref>{{cite journal 
|last1=Morello
|first1=L
|last2=Bardini
|first2=M
|last3=Sala
|first3=F
|last4=Breviario
|first4=D
|year=2002
|title=A long leader intron of the Ostub16 rice β-tubulin gene is required for high-level gene expression and can autonomously promote transcription both in vivo and in vitro
|journal=The Plant Journal
|volume=29
|issue=1
|pages=33–44
|doi=10.1046/j.0960-7412.2001.01192.x 
|pmid=12060225|doi-access=free
}}</ref> and ''[[Biology:Caenorhabditis elegans|C. elegans]].''<ref>{{cite journal 
|last1=Ho
|first1=SH
|last2=So
|first2=GMK
|last3=Chow
|first3=KL
|title=Postembryonic expression of Caenorhabditis elegans mab-21 and its requirement in sensory ray differentiation
|journal=Developmental Dynamics
|volume=221
|issue=4
|pages=422–430
|doi=10.1002/dvdy.1161 
|pmid=11500979 
|year=2001|s2cid=23197295
|doi-access=free
}}</ref> However, the mechanism(s) by which IME works are still not completely understood.<ref>{{Cite journal|title = The enduring mystery of intron-mediated enhancement|journal = Plant Science|date = 2015-08-01|issn = 1873-2259|pmid = 26089147|pages = 8–15|volume = 237|doi = 10.1016/j.plantsci.2015.04.017|first1 = Jenna E.|last1 = Gallegos|first2 = Alan B.|last2 = Rose}}</ref>

When testing to see whether any given intron enhances the expression of a gene, it is typical to compare the expression of two [[Biology:DNA construct|constructs]], one containing the intron and one without it, and to express the difference between the two results as a "[[Multiplication|fold increase]]" in enhancement. Further experiments can specifically point to IME as the cause of expression enhancement - one of the most common is to move the intron upstream of the transcription start site, removing it from the transcript. If the intron can no longer enhance expression, then inclusion of the intron in the transcript is important, and the intron probably causes IME.

Not all introns enhance gene expression, but those that do can enhance expression between 2– and >1,000–fold relative to an intronless control.<ref>{{cite journal 
|doi=10.1017/S1355838202020551 
|last1=Rose
|first1=A 
|year=2002 
|pages=1444–53 
|pmid=12458797
|issue=11
|title=Requirements for intron-mediated enhancement of gene expression in Arabidopsis
|journal=RNA 
|volume=8
|pmc=1370350}}</ref> In ''Arabidopsis'' and other plant species, the [http://korflab.ucdavis.edu/cgi-bin/IMEter_2014/web-imeter2.1.pl IMEter] has been developed to calculate the likelihood that an intron sequence will enhance gene expression.<ref>{{Cite journal|title = Promoter-Proximal Introns in Arabidopsis thaliana Are Enriched in Dispersed Signals that Elevate Gene Expression|url = http://www.plantcell.org/content/20/3/543|journal = The Plant Cell|date = 2008-03-01|issn = 1532-298X|pmc = 2329928|pmid = 18319396|pages = 543–551|volume = 20|issue = 3|doi = 10.1105/tpc.107.057190|language = en|first1 = Alan B.|last1 = Rose|first2 = Tali|last2 = Elfersi|first3 = Genis|last3 = Parra|first4 = Ian|last4 = Korf}}</ref> It does this by calculating a score based on the patterns of [[Biology:Nucleotide|nucleotide]] sequences within the target sequence. The position of an intron within the transcript is also important - the closer an intron is to the start (5' end) of a transcript, the greater its enhancement of gene expression.<ref>{{Cite journal|title = The effect of intron location on intron-mediated enhancement of gene expression in Arabidopsis|journal = The Plant Journal|date = 2004-12-01|issn = 1365-313X|pages = 744–751|volume = 40|issue = 5|doi = 10.1111/j.1365-313X.2004.02247.x|pmid = 15546357|language = en|first = Alan B.|last = Rose|doi-access = free}}</ref>

==References==
{{Reflist}}

{{DEFAULTSORT:Intron-Mediated Enhancement}}
[[Category:Gene expression]]

{{Sourceattribution|Intron-mediated enhancement}}