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===Cytoplasmic processing=== In the [[cytoplasm]], the pre-miRNA hairpin is cleaved by the RNase III enzyme [[Dicer]].<ref name="pmid17381281">{{cite journal | vauthors = Lund E, Dahlberg JE | title = Substrate selectivity of exportin 5 and Dicer in the biogenesis of microRNAs | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 71 | pages = 59β66 | year = 2006 | pmid = 17381281 | doi = 10.1101/sqb.2006.71.050 | doi-access = free }}</ref> This endoribonuclease interacts with 5' and 3' ends of the hairpin<ref>{{cite journal | vauthors = Park JE, Heo I, Tian Y, Simanshu DK, Chang H, Jee D, Patel DJ, Kim VN | title = Dicer recognizes the 5' end of RNA for efficient and accurate processing | journal = Nature | volume = 475 | issue = 7355 | pages = 201β05 | date = July 2011 | pmid = 21753850 | pmc = 4693635 | doi = 10.1038/nature10198 }}</ref> and cuts away the loop joining the 3' and 5' arms, yielding an imperfect miRNA:miRNA* duplex about 22 nucleotides in length.<ref name=pmid17381281/> Overall hairpin length and loop size influence the efficiency of Dicer processing. The imperfect nature of the miRNA:miRNA* pairing also affects cleavage.<ref name=pmid17381281/><ref name="pmid18268841">{{Cite book | vauthors = Ji X | chapter = The Mechanism of RNase III Action: How Dicer Dices | volume = 320 | pages = 99β116 | year = 2008 | pmid = 18268841 | doi = 10.1007/978-3-540-75157-1_5 | isbn = 978-3-540-75156-4 | series = Current Topics in Microbiology and Immunology | title = RNA Interference }}</ref> Some of the G-rich pre-miRNAs can potentially adopt the [[G-quadruplex]] structure as an alternative to the canonical hairpin structure. For example, human pre-miRNA 92b adopts a [[G-quadruplex]] structure which is resistant to the Dicer mediated cleavage in the [[cytoplasm]].<ref>{{cite journal | vauthors = Mirihana Arachchilage G, Dassanayake AC, Basu S | title = A potassium ion-dependent RNA structural switch regulates human pre-miRNA 92b maturation | journal = Chemistry & Biology | volume = 22 | issue = 2 | pages = 262β72 | date = February 2015 | pmid = 25641166 | doi = 10.1016/j.chembiol.2014.12.013 | doi-access = free }}</ref> Although either strand of the duplex may potentially act as a functional miRNA, only one strand is usually incorporated into the [[RNA-induced silencing complex]] (RISC) where the miRNA and its mRNA target interact. While the majority of miRNAs are located within the cell, some miRNAs, commonly known as circulating miRNAs or extracellular miRNAs, have also been found in extracellular environment, including various biological fluids and cell culture media.<ref>{{cite journal | doi = 10.1016/j.als.2016.11.007 | volume=10 | issue=2 | title=Extracellular/Circulating MicroRNAs: Release Mechanisms, Functions and Challenges | journal=Achievements in the Life Sciences | pages=175β186| year=2016 | vauthors = Sohel MH | doi-access=free }}</ref><ref name="Boeckel 616β617">{{cite journal | vauthors = Boeckel JN, Reis SM, Leistner D, ThomΓ© CE, Zeiher AM, Fichtlscherer S, Keller T | title = From heart to toe: heart's contribution on peripheral microRNA levels | journal = International Journal of Cardiology | volume = 172 | issue = 3 | pages = 616β17 | date = April 2014 | pmid = 24508494 | doi = 10.1016/j.ijcard.2014.01.082 }}</ref>
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