miR-1, miR-10b, miR-155, and miR-191 are novel regulators of BDNF

Brain-derived neurotrophic factor (BDNF) is a secreted protein of the neurotrophin family that regulates brain development, synaptogenesis, memory and learning, as well as development of peripheral organs, such as angiogenesis in the heart and postnatal growth and repair of skeletal muscle. However,...

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Main Authors:	Varendi, Kärt, Kumar, Anmol, Härma, Mari-Anne, Andressoo, Jaan-Olle
Format:	Online
Language:	English
Published:	Springer Basel 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207943/

id	pubmed-4207943
recordtype	oai_dc
spelling	pubmed-42079432014-10-28 miR-1, miR-10b, miR-155, and miR-191 are novel regulators of BDNF Varendi, Kärt Kumar, Anmol Härma, Mari-Anne Andressoo, Jaan-Olle Research Article Brain-derived neurotrophic factor (BDNF) is a secreted protein of the neurotrophin family that regulates brain development, synaptogenesis, memory and learning, as well as development of peripheral organs, such as angiogenesis in the heart and postnatal growth and repair of skeletal muscle. However, while precise regulation of BDNF levels is an important determinant in defining the biological outcome, the role of microRNAs (miRs) in modulating BDNF expression has not been extensively analyzed. Using in silico approaches, reporter systems, and analysis of endogenous BDNF, we show that miR-1, miR-10b, miR-155, and miR-191 directly repress BDNF through binding to their predicted sites in BDNF 3′UTR. We find that the overexpression of miR-1 and miR-10b suppresses endogenous BDNF protein levels and that silencing endogenous miR-10b increases BDNF mRNA and protein levels. Furthermore, we show that miR-1/206 binding sites within BDNF 3′UTR are used in differentiated myotubes but not in undifferentiated myoblasts. Finally, our data from two cell lines suggest that endogenous miR-1/206 and miR-10 family miRs act cooperatively in suppressing BDNF through their predicted sites in BDNF 3′UTR. In conclusion, our results highlight miR-1, miR-10b, miR-155, and miR-191 as novel regulators of BDNF long and short 3′UTR isoforms, supporting future research in different physiological and pathological contexts. Springer Basel 2014-05-08 2014 /pmc/articles/PMC4207943/ /pubmed/24804980 http://dx.doi.org/10.1007/s00018-014-1628-x Text en © The Author(s) 2014 Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Varendi, Kärt Kumar, Anmol Härma, Mari-Anne Andressoo, Jaan-Olle
spellingShingle	Varendi, Kärt Kumar, Anmol Härma, Mari-Anne Andressoo, Jaan-Olle miR-1, miR-10b, miR-155, and miR-191 are novel regulators of BDNF
author_facet	Varendi, Kärt Kumar, Anmol Härma, Mari-Anne Andressoo, Jaan-Olle
author_sort	Varendi, Kärt
title	miR-1, miR-10b, miR-155, and miR-191 are novel regulators of BDNF
title_short	miR-1, miR-10b, miR-155, and miR-191 are novel regulators of BDNF
title_full	miR-1, miR-10b, miR-155, and miR-191 are novel regulators of BDNF
title_fullStr	miR-1, miR-10b, miR-155, and miR-191 are novel regulators of BDNF
title_full_unstemmed	miR-1, miR-10b, miR-155, and miR-191 are novel regulators of BDNF
title_sort	mir-1, mir-10b, mir-155, and mir-191 are novel regulators of bdnf
description	Brain-derived neurotrophic factor (BDNF) is a secreted protein of the neurotrophin family that regulates brain development, synaptogenesis, memory and learning, as well as development of peripheral organs, such as angiogenesis in the heart and postnatal growth and repair of skeletal muscle. However, while precise regulation of BDNF levels is an important determinant in defining the biological outcome, the role of microRNAs (miRs) in modulating BDNF expression has not been extensively analyzed. Using in silico approaches, reporter systems, and analysis of endogenous BDNF, we show that miR-1, miR-10b, miR-155, and miR-191 directly repress BDNF through binding to their predicted sites in BDNF 3′UTR. We find that the overexpression of miR-1 and miR-10b suppresses endogenous BDNF protein levels and that silencing endogenous miR-10b increases BDNF mRNA and protein levels. Furthermore, we show that miR-1/206 binding sites within BDNF 3′UTR are used in differentiated myotubes but not in undifferentiated myoblasts. Finally, our data from two cell lines suggest that endogenous miR-1/206 and miR-10 family miRs act cooperatively in suppressing BDNF through their predicted sites in BDNF 3′UTR. In conclusion, our results highlight miR-1, miR-10b, miR-155, and miR-191 as novel regulators of BDNF long and short 3′UTR isoforms, supporting future research in different physiological and pathological contexts.
publisher	Springer Basel
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207943/
_version_	1613148308714291200

miR-1, miR-10b, miR-155, and miR-191 are novel regulators of BDNF

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