Editing MicroRNA (section)

===Mode of silencing and regulatory loops===
Gene silencing may occur either via mRNA degradation or preventing mRNA from being translated. For example, miR16 contains a sequence complementary to the [[AU-rich element]]<ref>{{Cite journal |last1=Shaw |first1=G. |last2=Kamen |first2=R. |date=1986-08-29 |title=A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation |url=https://pubmed.ncbi.nlm.nih.gov/3488815/ |journal=Cell |volume=46 |issue=5 |pages=659–667 |doi=10.1016/0092-8674(86)90341-7 |issn=0092-8674 |pmid=3488815}}</ref> found in the 3'UTR of many unstable mRNAs, such as [[Tumor necrosis factor alpha|TNF alpha]] or [[Granulocyte macrophage colony-stimulating factor|GM-CSF]].<ref name="Jing Q, Huang S, Guth S, Zarubin T, Motoyama A, Chen J, Di Padova F, Lin SC, Gram H, Han J 2005 623-34">{{cite journal | vauthors = Jing Q, Huang S, Guth S, Zarubin T, Motoyama A, Chen J, Di Padova F, Lin SC, Gram H, Han J | title = Involvement of microRNA in AU-rich element-mediated mRNA instability | journal = Cell | volume = 120 | issue = 5 | pages = 623–34 | date = March 2005 | pmid = 15766526 | doi = 10.1016/j.cell.2004.12.038 | doi-access = free }}</ref> It has been demonstrated that given complete complementarity between the miRNA and target mRNA sequence, Ago2 can cleave the mRNA and lead to direct mRNA degradation. In the absence of complementarity, silencing is achieved by preventing translation.<ref name="pmid15685193"/> The relation of miRNA and its target mRNA can be based on the simple negative regulation of a target mRNA, but it seems that a common scenario is the use of a "coherent [[Feed forward (control)|feed-forward]] loop", "mutual negative feedback loop" (also termed double negative loop) and "positive feedback/feed-forward loop". Some miRNAs work as buffers of random gene expression changes arising due to stochastic events in transcription, translation and protein stability. Such regulation is typically achieved by the virtue of negative feedback loops or incoherent feed-forward loop uncoupling protein output from mRNA transcription.