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Differential Inhibition of Target Gene Expression by Human microRNAs

microRNAs (miRNAs) exert their functions by repressing the expression of their target genes, but most miRNA target genes are unknown, and the degree to which a miRNA differentially inhibits the expression of its targets is underappreciated. We selected human miR-1, miR-122, and miR-124 as representa...

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Detalles Bibliográficos
Autores principales: Li, Peng, Chen, Yi, Juma, Conslata Awino, Yang, Chengyong, Huang, Jinfeng, Zhang, Xiaoxiao, Zeng, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721455/
https://www.ncbi.nlm.nih.gov/pubmed/31366019
http://dx.doi.org/10.3390/cells8080791
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author Li, Peng
Chen, Yi
Juma, Conslata Awino
Yang, Chengyong
Huang, Jinfeng
Zhang, Xiaoxiao
Zeng, Yan
author_facet Li, Peng
Chen, Yi
Juma, Conslata Awino
Yang, Chengyong
Huang, Jinfeng
Zhang, Xiaoxiao
Zeng, Yan
author_sort Li, Peng
collection PubMed
description microRNAs (miRNAs) exert their functions by repressing the expression of their target genes, but most miRNA target genes are unknown, and the degree to which a miRNA differentially inhibits the expression of its targets is underappreciated. We selected human miR-1, miR-122, and miR-124 as representatives to investigate the reliability of miRNA target predictions and examine how miRNAs suppress their targets. We constructed miRNA target gene reporter libraries based on prediction programs TargetScan, miRanda, and PicTar, and performed large-scale reporter assays to directly evaluate whether and how strongly a predicted target gene is repressed by its miRNA. We then performed statistical analyses to examine parameters that contributed to the miRNA inhibition of target genes. We found that the three programs have approximately 72–85% success rates in predicting genuine targets and that the miRNA inhibition of different targets varies in extent. We also identified parameters that could predict the degrees of miRNA repression, and further showed that differential miR-124 repression might contribute to differential gene expression in vivo. Our studies systematically investigated hundreds of miRNA target genes, shed light on factors influencing miRNA functions, and suggested a new mechanism by which differential target repression by miRNAs regulates endogenous gene expression.
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spelling pubmed-67214552019-09-10 Differential Inhibition of Target Gene Expression by Human microRNAs Li, Peng Chen, Yi Juma, Conslata Awino Yang, Chengyong Huang, Jinfeng Zhang, Xiaoxiao Zeng, Yan Cells Article microRNAs (miRNAs) exert their functions by repressing the expression of their target genes, but most miRNA target genes are unknown, and the degree to which a miRNA differentially inhibits the expression of its targets is underappreciated. We selected human miR-1, miR-122, and miR-124 as representatives to investigate the reliability of miRNA target predictions and examine how miRNAs suppress their targets. We constructed miRNA target gene reporter libraries based on prediction programs TargetScan, miRanda, and PicTar, and performed large-scale reporter assays to directly evaluate whether and how strongly a predicted target gene is repressed by its miRNA. We then performed statistical analyses to examine parameters that contributed to the miRNA inhibition of target genes. We found that the three programs have approximately 72–85% success rates in predicting genuine targets and that the miRNA inhibition of different targets varies in extent. We also identified parameters that could predict the degrees of miRNA repression, and further showed that differential miR-124 repression might contribute to differential gene expression in vivo. Our studies systematically investigated hundreds of miRNA target genes, shed light on factors influencing miRNA functions, and suggested a new mechanism by which differential target repression by miRNAs regulates endogenous gene expression. MDPI 2019-07-30 /pmc/articles/PMC6721455/ /pubmed/31366019 http://dx.doi.org/10.3390/cells8080791 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Peng
Chen, Yi
Juma, Conslata Awino
Yang, Chengyong
Huang, Jinfeng
Zhang, Xiaoxiao
Zeng, Yan
Differential Inhibition of Target Gene Expression by Human microRNAs
title Differential Inhibition of Target Gene Expression by Human microRNAs
title_full Differential Inhibition of Target Gene Expression by Human microRNAs
title_fullStr Differential Inhibition of Target Gene Expression by Human microRNAs
title_full_unstemmed Differential Inhibition of Target Gene Expression by Human microRNAs
title_short Differential Inhibition of Target Gene Expression by Human microRNAs
title_sort differential inhibition of target gene expression by human micrornas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721455/
https://www.ncbi.nlm.nih.gov/pubmed/31366019
http://dx.doi.org/10.3390/cells8080791
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