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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6721455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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