Journal
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume 69, Issue -, Pages 75-84Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2015.10.006
Keywords
Lymphatic endothelial cells; microRNA; RNA-binding proteins; AGO2; miR-132
Categories
Funding
- Combating Infectious Disease: Computational Approaches in Translational Science Wellcome Trust PhD programme [WT095024MA]
- Medical Research Council [MR/L008505/1]
- Wellcome Trust through the Centre for Chronic Diseases and Disorders at the University of York [097829]
- Biotechnology and Biological Sciences Research Council Doctoral Training Programme in Mechanistic Biology and its Strategic Application [BB/J01113/1]
- BBSRC [BB/I007571/2]
- Biotechnology and Biological Sciences Research Council [BB/L027755/1, BB/I007571/2, BB/I007571/1, 1504182] Funding Source: researchfish
- Cancer Research UK [12733] Funding Source: researchfish
- Medical Research Council [MR/L008505/1] Funding Source: researchfish
- BBSRC [BB/L027755/1, BB/I007571/1, BB/I007571/2] Funding Source: UKRI
- MRC [MR/L008505/1] Funding Source: UKRI
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The abundance of miR-132 ranges from constitutively high in the brain where it is necessary for neuronal development and function, to inducible expression in haematopoietic and endothelial cells where it controls angiogenesis and immune activation. We show that expression of AGO2, a protein central to miRNA-mediated gene silencing and miRNA biogenesis, is negatively regulated by miR-132. Using HeLa cells, we demonstrate that miR-132 interacts with the AGO2 mRNA 3'UTR and suppresses AGO2 expression and AGO2-dependent small RNA-mediated silencing. Similarly, miR-132 over-expression leads to AGO2 suppression in primary human dermal lymphatic endothelial cells (HDLECs). During phorbol myristate acetate (PMA)-activation of HDLECs, miR-132 is induced in a CREB-dependent manner and inhibition of miR-132 results in increased AGO2 expression. In agreement with the role of AGO2 in maintenance of miRNA expression, AGO2 suppression by miR-132 affects the steady state levels of miR-221 and miR-146a, two miRNAs involved in angiogenesis and inflammation, respectively. Our data demonstrate that the miRNA-silencing machinery is subject to autoregulation during primary cell activation through direct suppression of AGO2 by miR-132. (C) 2015 The Authors. Published by Elsevier Ltd.
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