Increased hippocampal excitability in miR-324-null mice

Abstract MicroRNAs are non-coding RNAs that act to downregulate the expression of target genes by translational repression and degradation of messenger RNA molecules. Individual microRNAs have the ability to specifically target a wide array of gene transcripts, therefore allowing each microRNA to pl...

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Autores principales: Dan J. Hayman, Tamara Modebadze, Sarah Charlton, Kat Cheung, Jamie Soul, Hua Lin, Yao Hao, Colin G. Miles, Dimitra Tsompani, Robert M. Jackson, Michael D. Briggs, Katarzyna A. Piróg, Ian M. Clark, Matt J. Barter, Gavin J. Clowry, Fiona E. N. LeBeau, David A. Young
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/b74a1a1210eb465eb49f8ba80fb52c10
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spelling oai:doaj.org-article:b74a1a1210eb465eb49f8ba80fb52c102021-12-02T15:53:10ZIncreased hippocampal excitability in miR-324-null mice10.1038/s41598-021-89874-12045-2322https://doaj.org/article/b74a1a1210eb465eb49f8ba80fb52c102021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89874-1https://doaj.org/toc/2045-2322Abstract MicroRNAs are non-coding RNAs that act to downregulate the expression of target genes by translational repression and degradation of messenger RNA molecules. Individual microRNAs have the ability to specifically target a wide array of gene transcripts, therefore allowing each microRNA to play key roles in multiple biological pathways. miR-324 is a microRNA predicted to target thousands of RNA transcripts and is expressed far more highly in the brain than in any other tissue, suggesting that it may play a role in one or multiple neurological pathways. Here we present data from the first global miR-324-null mice, in which increased excitability and interictal discharges were identified in vitro in the hippocampus. RNA sequencing was used to identify differentially expressed genes in miR-324-null mice which may contribute to this increased hippocampal excitability, and 3′UTR luciferase assays and western blotting revealed that two of these, Suox and Cd300lf, are novel direct targets of miR-324. Characterisation of microRNAs that produce an effect on neurological activity, such as miR-324, and identification of the pathways they regulate will allow a better understanding of the processes involved in normal neurological function and in turn may present novel pharmaceutical targets in treating neurological disease.Dan J. HaymanTamara ModebadzeSarah CharltonKat CheungJamie SoulHua LinYao HaoColin G. MilesDimitra TsompaniRobert M. JacksonMichael D. BriggsKatarzyna A. PirógIan M. ClarkMatt J. BarterGavin J. ClowryFiona E. N. LeBeauDavid A. YoungNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Dan J. Hayman
Tamara Modebadze
Sarah Charlton
Kat Cheung
Jamie Soul
Hua Lin
Yao Hao
Colin G. Miles
Dimitra Tsompani
Robert M. Jackson
Michael D. Briggs
Katarzyna A. Piróg
Ian M. Clark
Matt J. Barter
Gavin J. Clowry
Fiona E. N. LeBeau
David A. Young
Increased hippocampal excitability in miR-324-null mice
description Abstract MicroRNAs are non-coding RNAs that act to downregulate the expression of target genes by translational repression and degradation of messenger RNA molecules. Individual microRNAs have the ability to specifically target a wide array of gene transcripts, therefore allowing each microRNA to play key roles in multiple biological pathways. miR-324 is a microRNA predicted to target thousands of RNA transcripts and is expressed far more highly in the brain than in any other tissue, suggesting that it may play a role in one or multiple neurological pathways. Here we present data from the first global miR-324-null mice, in which increased excitability and interictal discharges were identified in vitro in the hippocampus. RNA sequencing was used to identify differentially expressed genes in miR-324-null mice which may contribute to this increased hippocampal excitability, and 3′UTR luciferase assays and western blotting revealed that two of these, Suox and Cd300lf, are novel direct targets of miR-324. Characterisation of microRNAs that produce an effect on neurological activity, such as miR-324, and identification of the pathways they regulate will allow a better understanding of the processes involved in normal neurological function and in turn may present novel pharmaceutical targets in treating neurological disease.
format article
author Dan J. Hayman
Tamara Modebadze
Sarah Charlton
Kat Cheung
Jamie Soul
Hua Lin
Yao Hao
Colin G. Miles
Dimitra Tsompani
Robert M. Jackson
Michael D. Briggs
Katarzyna A. Piróg
Ian M. Clark
Matt J. Barter
Gavin J. Clowry
Fiona E. N. LeBeau
David A. Young
author_facet Dan J. Hayman
Tamara Modebadze
Sarah Charlton
Kat Cheung
Jamie Soul
Hua Lin
Yao Hao
Colin G. Miles
Dimitra Tsompani
Robert M. Jackson
Michael D. Briggs
Katarzyna A. Piróg
Ian M. Clark
Matt J. Barter
Gavin J. Clowry
Fiona E. N. LeBeau
David A. Young
author_sort Dan J. Hayman
title Increased hippocampal excitability in miR-324-null mice
title_short Increased hippocampal excitability in miR-324-null mice
title_full Increased hippocampal excitability in miR-324-null mice
title_fullStr Increased hippocampal excitability in miR-324-null mice
title_full_unstemmed Increased hippocampal excitability in miR-324-null mice
title_sort increased hippocampal excitability in mir-324-null mice
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/b74a1a1210eb465eb49f8ba80fb52c10
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