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microRNAs regulate cell-to-cell variability of endogenous target gene expression in developing mouse thymocytes

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Item Type:Article
Title:microRNAs regulate cell-to-cell variability of endogenous target gene expression in developing mouse thymocytes
Creators Name:Blevins, R. and Bruno, L. and Carroll, T. and Elliott, J. and Marcais, A. and Loh, C. and Hertweck, A. and Krek, A. and Rajewsky, N. and Chen, C.Z. and Fisher, A.G. and Merkenschlager, M.
Abstract:The development and homeostasis of multicellular organisms relies on gene regulation within individual constituent cells. Gene regulatory circuits that increase the robustness of gene expression frequently incorporate microRNAs as post-transcriptional regulators. Computational approaches, synthetic gene circuits and observations in model organisms predict that the co-regulation of microRNAs and their target mRNAs can reduce cell-to-cell variability in the expression of target genes. However, whether microRNAs directly regulate variability of endogenous gene expression remains to be tested in mammalian cells. Here we use quantitative flow cytometry to show that microRNAs impact on cell-to-cell variability of protein expression in developing mouse thymocytes. We find two distinct mechanisms that control variation in the activation-induced expression of the microRNA target CD69. First, the expression of miR-17 and miR-20a, two members of the miR-17-92 cluster, is co-regulated with the target mRNA Cd69 to form an activation-induced incoherent feed-forward loop. Another microRNA, miR-181a, acts at least in part upstream of the target mRNA Cd69 to modulate cellular responses to activation. The ability of microRNAs to render gene expression more uniform across mammalian cell populations may be important for normal development and for disease.
Keywords:Cell Survival, Developmental Gene Expression Regulation, Flow Cytometry, Hematopoiesis, Messenger RNA, MicroRNAs, Protein Biosynthesis, Thymocytes, Tumor Cell Line, Animals, Mice
Source:PLoS Genetics
Publisher:Public Library of Science
Page Range:e1005020
Date:25 February 2015
Official Publication:https://doi.org/10.1371/journal.pgen.1005020
PubMed:View item in PubMed

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