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MiR34a Regulates Neuronal MHC Class I Molecules and Promotes Primary Hippocampal Neuron Dendritic Growth and Branching

In the immune system, Major Histocompatibility Complex class I (MHC-I) molecules are located on the surface of most nucleated cells in vertebrates where they mediate immune responses. Accumulating evidence indicates that MHC-I molecules are also expressed in the central nervous system (CNS) where th...

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Autores principales: Hu, Yue, Pei, Wenqin, Hu, Ying, Li, Ping, Sun, Chen, Du, Jiawei, Zhang, Ying, Miao, Fengqin, Zhang, Aifeng, Shen, Yuqing, Zhang, Jianqiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655649/
https://www.ncbi.nlm.nih.gov/pubmed/33192317
http://dx.doi.org/10.3389/fncel.2020.573208
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author Hu, Yue
Pei, Wenqin
Hu, Ying
Li, Ping
Sun, Chen
Du, Jiawei
Zhang, Ying
Miao, Fengqin
Zhang, Aifeng
Shen, Yuqing
Zhang, Jianqiong
author_facet Hu, Yue
Pei, Wenqin
Hu, Ying
Li, Ping
Sun, Chen
Du, Jiawei
Zhang, Ying
Miao, Fengqin
Zhang, Aifeng
Shen, Yuqing
Zhang, Jianqiong
author_sort Hu, Yue
collection PubMed
description In the immune system, Major Histocompatibility Complex class I (MHC-I) molecules are located on the surface of most nucleated cells in vertebrates where they mediate immune responses. Accumulating evidence indicates that MHC-I molecules are also expressed in the central nervous system (CNS) where they play important roles that are significantly different from their immune functions. Classical MHC-I molecules are temporally and spatially expressed in the developing and adult CNS, where they participate in the synaptic formation, remodeling and plasticity. Therefore, clarifying the regulation of MHC-I expression is necessary to develop an accurate understanding of its function in the CNS. Here, we show that microRNA 34a (miR34a), a brain enriched noncoding RNA, is temporally expressed in developing hippocampal neurons, and its expression is significantly increased after MHC-I protein abundance is decreased in the hippocampus. Computational algorithms identify putative miR34a target sites in the 3′UTR of MHC-I mRNA, and here we demonstrate direct targeting of miR34a to MHC-I mRNA using a dual-luciferase reporter assay system. MiR34a targeting can decrease constitutive MHC-I expression in both Neuro-2a neuroblastoma cells and primary hippocampal neurons. Finally, miR34a mediated reduction of MHC-I results in increased dendritic growth and branching in cultured hippocampal neurons. Taken together, our findings identify miR34a as a novel regulator of MHC-I for shaping neural morphology in developing hippocampal neurons.
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spelling pubmed-76556492020-11-13 MiR34a Regulates Neuronal MHC Class I Molecules and Promotes Primary Hippocampal Neuron Dendritic Growth and Branching Hu, Yue Pei, Wenqin Hu, Ying Li, Ping Sun, Chen Du, Jiawei Zhang, Ying Miao, Fengqin Zhang, Aifeng Shen, Yuqing Zhang, Jianqiong Front Cell Neurosci Cellular Neuroscience In the immune system, Major Histocompatibility Complex class I (MHC-I) molecules are located on the surface of most nucleated cells in vertebrates where they mediate immune responses. Accumulating evidence indicates that MHC-I molecules are also expressed in the central nervous system (CNS) where they play important roles that are significantly different from their immune functions. Classical MHC-I molecules are temporally and spatially expressed in the developing and adult CNS, where they participate in the synaptic formation, remodeling and plasticity. Therefore, clarifying the regulation of MHC-I expression is necessary to develop an accurate understanding of its function in the CNS. Here, we show that microRNA 34a (miR34a), a brain enriched noncoding RNA, is temporally expressed in developing hippocampal neurons, and its expression is significantly increased after MHC-I protein abundance is decreased in the hippocampus. Computational algorithms identify putative miR34a target sites in the 3′UTR of MHC-I mRNA, and here we demonstrate direct targeting of miR34a to MHC-I mRNA using a dual-luciferase reporter assay system. MiR34a targeting can decrease constitutive MHC-I expression in both Neuro-2a neuroblastoma cells and primary hippocampal neurons. Finally, miR34a mediated reduction of MHC-I results in increased dendritic growth and branching in cultured hippocampal neurons. Taken together, our findings identify miR34a as a novel regulator of MHC-I for shaping neural morphology in developing hippocampal neurons. Frontiers Media S.A. 2020-10-28 /pmc/articles/PMC7655649/ /pubmed/33192317 http://dx.doi.org/10.3389/fncel.2020.573208 Text en Copyright © 2020 Hu, Pei, Hu, Li, Sun, Du, Zhang, Miao, Zhang, Shen and Zhang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular Neuroscience
Hu, Yue
Pei, Wenqin
Hu, Ying
Li, Ping
Sun, Chen
Du, Jiawei
Zhang, Ying
Miao, Fengqin
Zhang, Aifeng
Shen, Yuqing
Zhang, Jianqiong
MiR34a Regulates Neuronal MHC Class I Molecules and Promotes Primary Hippocampal Neuron Dendritic Growth and Branching
title MiR34a Regulates Neuronal MHC Class I Molecules and Promotes Primary Hippocampal Neuron Dendritic Growth and Branching
title_full MiR34a Regulates Neuronal MHC Class I Molecules and Promotes Primary Hippocampal Neuron Dendritic Growth and Branching
title_fullStr MiR34a Regulates Neuronal MHC Class I Molecules and Promotes Primary Hippocampal Neuron Dendritic Growth and Branching
title_full_unstemmed MiR34a Regulates Neuronal MHC Class I Molecules and Promotes Primary Hippocampal Neuron Dendritic Growth and Branching
title_short MiR34a Regulates Neuronal MHC Class I Molecules and Promotes Primary Hippocampal Neuron Dendritic Growth and Branching
title_sort mir34a regulates neuronal mhc class i molecules and promotes primary hippocampal neuron dendritic growth and branching
topic Cellular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655649/
https://www.ncbi.nlm.nih.gov/pubmed/33192317
http://dx.doi.org/10.3389/fncel.2020.573208
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