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Global and Local Competition between Exogenously Introduced microRNAs and Endogenously Expressed microRNAs

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Title
Global and Local Competition between Exogenously Introduced microRNAs and Endogenously Expressed microRNAs
Author(s)
Doyeon Kim; Jongkyu Kim; Daehyun Baek
Subject
competition, microRNA, miRNA targeting, shRNA, siRNA
Publication Date
2014-05
Journal
MOLECULES AND CELLS, v.37, no.5, pp.412 - 417
Publisher
KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
Abstract
It has been reported that exogenously introduced micro-RNA (exo-miRNA) competes with endogenously expressed miRNAs (endo-miRNAs) in human cells, resulting in a detectable upregulation of mRNAs with endo-miRNA target sites (TSs). However, the detailed mechanisms of the competition between exo- and endo-miRNAs remain uninvestigated. In this study, using 74 microarrays that monitored the whole-transcriptome response after introducing miRNAs or siRNAs into HeLa cells, we systematically examined the derepression of mRNAs with exoand/or endo-miRNA TSs.We quantitatively assessed the effect of the number of endo-miRNA TSs on the degree of mRNA derepression. As a result, we observed that the number of endo-miRNA TSs was significantly associated with the degree of derepression, supporting that the derepression resulted from the competition between exo- and endo-miRNAs. However, when we examined whether the site proficiency of exomiRNA TSs could also influence mRNA derepression, to our surprise, we discovered a strong positive correlation. Our analysis indicates that site proficiencies of both exoand endo-miRNA TSs are important determinants for the degree of mRNA derepression, implying that the derepression of mRNAs in response to exo-miRNA is more complex than that currently perceived. Our observations may lead to a more complete understanding of the detailed mechanisms of the competition between exo- and endo-miRNAs and to a more accurate prediction of miRNA targets. Our analysis also suggests an interesting hypothesis that long 3-UTRs may function as molecular buffer against gene expression regulation by individual miRNAs.
URI
https://pr.ibs.re.kr/handle/8788114/1033
DOI
10.14348/molcells.2014.0100
ISSN
1016-8478
Appears in Collections:
Center for RNA Research(RNA 연구단) > 1. Journal Papers (저널논문)
Files in This Item:
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