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==Targets== Plant miRNAs usually have near-perfect pairing with their mRNA targets, which induces gene repression through cleavage of the target transcripts.<ref name="ReferenceA">{{cite journal | vauthors = Jones-Rhoades MW, Bartel DP, Bartel B | title = MicroRNAS and their regulatory roles in plants | journal = Annual Review of Plant Biology | volume = 57 | pages = 19–53 | date = 2006 | pmid = 16669754 | doi = 10.1146/annurev.arplant.57.032905.105218 }}</ref><ref>{{cite journal |vauthors=Hunt M, Banerjee S, Surana P, Liu M, Fuerst G, Mathioni S, Meyers BC, Nettleton D, Wise RP |title=Small RNA discovery in the interaction between barley and the powdery mildew pathogen |journal=BMC Genomics |volume=20 |pages=19–53 |date=2019 |issue=1 |doi=10.1186/s12864-019-5947-z |pmid=31345162 |pmc=6657096 |doi-access=free }}</ref> In contrast, animal miRNAs are able to recognize their target mRNAs by using as few as 6–8 nucleotides (the seed region) at the 5' end of the miRNA,<ref name="Lewis BP, Burge CB, Bartel DP 2005 15–20" /><ref name="Lewis BP, Shih IH, Jones-Rhoades M, Bartel DP, Burge CB 2003 787–798">{{cite journal | vauthors = Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB | title = Prediction of mammalian microRNA targets | journal = Cell | volume = 115 | issue = 7 | pages = 787–98 | date = December 2003 | pmid = 14697198 | doi = 10.1016/S0092-8674(03)01018-3 | doi-access = free }}</ref><ref name="Ellwanger DC, Büttner FA, Mewes HW, Stümpflen V 2011 1346-50">{{cite journal | vauthors = Ellwanger DC, Büttner FA, Mewes HW, Stümpflen V | title = The sufficient minimal set of miRNA seed types | journal = Bioinformatics | volume = 27 | issue = 10 | pages = 1346–50 | date = May 2011 | pmid = 21441577 | pmc = 3087955 | doi = 10.1093/bioinformatics/btr149 }}</ref> which is not enough pairing to induce cleavage of the target mRNAs.<ref name="pmid19167326" /> Combinatorial regulation is a feature of miRNA regulation in animals.<ref name="pmid19167326" /><ref>{{cite journal | vauthors = Rajewsky N | title = microRNA target predictions in animals | journal = Nature Genetics | volume = 38 | issue = 6s | pages = S8–13 | date = June 2006 | pmid = 16736023 | doi = 10.1038/ng1798 | s2cid = 23496396 }}</ref> A given miRNA may have hundreds of different mRNA targets, and a given target might be regulated by multiple miRNAs.<ref name="pmid18955434" /><ref>{{cite journal | vauthors = Krek A, Grün D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N | title = Combinatorial microRNA target predictions | journal = Nature Genetics | volume = 37 | issue = 5 | pages = 495–500 | date = May 2005 | pmid = 15806104 | doi = 10.1038/ng1536 | s2cid = 22672750 }}</ref> Estimates of the average number of unique messenger RNAs that are targets for repression by a typical miRNA vary, depending on the estimation method,<ref>{{cite journal | vauthors = Thomson DW, Bracken CP, Goodall GJ | title = Experimental strategies for microRNA target identification | journal = Nucleic Acids Research | volume = 39 | issue = 16 | pages = 6845–53 | date = September 2011 | pmid = 21652644 | pmc = 3167600 | doi = 10.1093/nar/gkr330 }}</ref> but multiple approaches show that mammalian miRNAs can have many unique targets. For example, an analysis of the miRNAs highly conserved in vertebrates shows that each has, on average, roughly 400 conserved targets.<ref name="pmid18955434" /> Likewise, experiments show that a single miRNA species can reduce the stability of hundreds of unique messenger RNAs.<ref name="pmid15685193">{{cite journal | vauthors = Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM | title = Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs | journal = Nature | volume = 433 | issue = 7027 | pages = 769–73 | date = February 2005 | pmid = 15685193 | doi = 10.1038/nature03315 | bibcode = 2005Natur.433..769L | s2cid = 4430576 }}</ref> Other experiments show that a single miRNA species may repress the production of hundreds of proteins, but that this repression often is relatively mild (much less than 2-fold).<ref>{{cite journal | vauthors = Selbach M, Schwanhäusser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N | title = Widespread changes in protein synthesis induced by microRNAs | journal = Nature | volume = 455 | issue = 7209 | pages = 58–63 | date = September 2008 | pmid = 18668040 | doi = 10.1038/nature07228 | bibcode = 2008Natur.455...58S | s2cid = 4429008 }}</ref><ref>{{cite journal | vauthors = Baek D, Villén J, Shin C, Camargo FD, Gygi SP, Bartel DP | title = The impact of microRNAs on protein output | journal = Nature | volume = 455 | issue = 7209 | pages = 64–71 | date = September 2008 | pmid = 18668037 | pmc = 2745094 | doi = 10.1038/nature07242 | bibcode = 2008Natur.455...64B }}</ref>
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