miRNA Enriched in Human Neuroblast Nuclei Bind the MAZ Transcription Factor and Their Precursors Contain the MAZ Consensus Motif
While the cytoplasmic function of microRNA (miRNA) as post-transcriptional regulators of mRNA has been the subject of significant research effort, their activity in the nucleus is less well characterized. Here we use a human neuronal cell model to show that some mature miRNA are preferentially enric...
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| Published in | Frontiers in molecular neuroscience Vol. 10; p. 259 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Switzerland
Frontiers Research Foundation
21.08.2017
Frontiers Media S.A |
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| Online Access | Get full text |
| ISSN | 1662-5099 1662-5099 |
| DOI | 10.3389/fnmol.2017.00259 |
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| Abstract | While the cytoplasmic function of microRNA (miRNA) as post-transcriptional regulators of mRNA has been the subject of significant research effort, their activity in the nucleus is less well characterized. Here we use a human neuronal cell model to show that some mature miRNA are preferentially enriched in the nucleus. These molecules were predominantly primate-specific and contained a sequence motif with homology to the consensus MAZ transcription factor binding element. Precursor miRNA containing this motif were shown to have affinity for MAZ protein in nuclear extract. We then used Ago1/2 RIP-Seq to explore nuclear miRNA-associated mRNA targets. Interestingly, the genes for Ago2-associated transcripts were also significantly enriched with MAZ binding sites and neural function, whereas Ago1-transcripts were associated with general metabolic processes and localized with SC35 spliceosomes. These findings suggest the MAZ transcription factor is associated with miRNA in the nucleus and may influence the regulation of neuronal development through Ago2-associated miRNA induced silencing complexes. The MAZ transcription factor may therefore be important for organizing higher order integration of transcriptional and post-transcriptional processes in primate neurons. |
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| AbstractList | While the cytoplasmic function of microRNA (miRNA) as post-transcriptional regulators of mRNA has been the subject of significant research effort, their activity in the nucleus is less well characterized. Here we use a human neuronal cell model to show that some mature miRNA are preferentially enriched in the nucleus. These molecules were predominantly primate-specific and contained a sequence motif with homology to the consensus MAZ transcription factor binding element. Precursor miRNA containing this motif were shown to have affinity for MAZ protein in nuclear extract. We then used Ago1/2 RIP-Seq to explore nuclear miRNA-associated mRNA targets. Interestingly, the genes for Ago2-associated transcripts were also significantly enriched with MAZ binding sites and neural function, whereas Ago1-transcripts were associated with general metabolic processes and localized with SC35 spliceosomes. These findings suggest the MAZ transcription factor is associated with miRNA in the nucleus and may influence the regulation of neuronal development through Ago2-associated miRNA induced silencing complexes. The MAZ transcription factor may therefore be important for organizing higher order integration of transcriptional and post-transcriptional processes in primate neurons. While the cytoplasmic function of microRNA (miRNA) as post-transcriptional regulators of mRNA has been the subject of significant research effort, their activity in the nucleus is less well characterized. Here we use a human neuronal cell model to show that some mature miRNA are preferentially enriched in the nucleus. These molecules were predominantly primate-specific and contained a sequence motif with homology to the consensus MAZ transcription factor binding element. Precursor miRNA containing this motif were shown to have affinity for MAZ protein in nuclear extract. We then used Ago1/2 RIP-Seq to explore nuclear miRNA-associated mRNA targets. Interestingly, the genes for Ago2-associated transcripts were also significantly enriched with MAZ binding sites and neural function, whereas Ago1-transcripts were associated with general metabolic processes and localized with SC35 spliceosomes. These findings suggest the MAZ transcription factor is associated with miRNA in the nucleus and may influence the regulation of neuronal development through Ago2-associated miRNA induced silencing complexes. The MAZ transcription factor may therefore be important for organizing higher order integration of transcriptional and post-transcriptional processes in primate neurons.While the cytoplasmic function of microRNA (miRNA) as post-transcriptional regulators of mRNA has been the subject of significant research effort, their activity in the nucleus is less well characterized. Here we use a human neuronal cell model to show that some mature miRNA are preferentially enriched in the nucleus. These molecules were predominantly primate-specific and contained a sequence motif with homology to the consensus MAZ transcription factor binding element. Precursor miRNA containing this motif were shown to have affinity for MAZ protein in nuclear extract. We then used Ago1/2 RIP-Seq to explore nuclear miRNA-associated mRNA targets. Interestingly, the genes for Ago2-associated transcripts were also significantly enriched with MAZ binding sites and neural function, whereas Ago1-transcripts were associated with general metabolic processes and localized with SC35 spliceosomes. These findings suggest the MAZ transcription factor is associated with miRNA in the nucleus and may influence the regulation of neuronal development through Ago2-associated miRNA induced silencing complexes. The MAZ transcription factor may therefore be important for organizing higher order integration of transcriptional and post-transcriptional processes in primate neurons. While the cytoplasmic function of microRNA (miRNA) as post-transcriptional regulators of mRNA has been the subject of significant research effort, their activity in the nucleus is less well characterised. Here we use a human neuronal cell model to show that some mature miRNA are preferentially enriched in the nucleus. These molecules were predominantly primate specific and contained a sequence motif with homology to the consensus MAZ transcription factor-binding element. Precursor miRNA containing this motif were shown to have affinity for MAZ protein in nuclear extract. We then used Ago1/2 RIP-Seq to explore nuclear miRNA-associated mRNA targets. Interestingly, the genes for Ago2-associated transcripts were also significantly enriched with MAZ binding sites and neural function, whereas Ago1-transcripts were associated with general metabolic processes and localized with Sc35 spliceosomes. These findings suggest the MAZ transcription factor is associated with miRNA in the nucleus and may influence the regulation of neuronal development through Ago2-associated miRNA induced silencing complexes (miRISC). The MAZ transcription factor may therefore be important for organizing higher order integration of transcriptional and posttranscriptional processes in primate neurons. |
| Author | Wang, Dan O. Goldie, Belinda J. Cairns, Murray J. Weidenhofer, Judith Fitzsimmons, Chantel Atkins, Joshua R. |
| AuthorAffiliation | 1 School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan NSW, Australia 3 World Premier International Research Center – Institute for Integrated Cell-Material Sciences, Kyoto University Kyoto, Japan 2 Centre for Brain and Mental Health Research, Hunter Medical Research Institute, The University of Newcastle, Callaghan NSW, Australia 4 The Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research Kyoto, Japan |
| AuthorAffiliation_xml | – name: 1 School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan NSW, Australia – name: 4 The Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research Kyoto, Japan – name: 2 Centre for Brain and Mental Health Research, Hunter Medical Research Institute, The University of Newcastle, Callaghan NSW, Australia – name: 3 World Premier International Research Center – Institute for Integrated Cell-Material Sciences, Kyoto University Kyoto, Japan |
| Author_xml | – sequence: 1 givenname: Belinda J. surname: Goldie fullname: Goldie, Belinda J. – sequence: 2 givenname: Chantel surname: Fitzsimmons fullname: Fitzsimmons, Chantel – sequence: 3 givenname: Judith surname: Weidenhofer fullname: Weidenhofer, Judith – sequence: 4 givenname: Joshua R. surname: Atkins fullname: Atkins, Joshua R. – sequence: 5 givenname: Dan O. surname: Wang fullname: Wang, Dan O. – sequence: 6 givenname: Murray J. surname: Cairns fullname: Cairns, Murray J. |
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| CitedBy_id | crossref_primary_10_1155_2020_2638130 crossref_primary_10_3389_fimmu_2023_1097491 crossref_primary_10_3390_genes11050482 crossref_primary_10_1016_j_celrep_2020_107795 |
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| Copyright | 2017. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Copyright © 2017 Goldie, Fitzsimmons, Weidenhofer, Atkins, Wang and Cairns. 2017 Goldie, Fitzsimmons, Weidenhofer, Atkins, Wang and Cairns |
| Copyright_xml | – notice: 2017. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: Copyright © 2017 Goldie, Fitzsimmons, Weidenhofer, Atkins, Wang and Cairns. 2017 Goldie, Fitzsimmons, Weidenhofer, Atkins, Wang and Cairns |
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| Keywords | regulation of gene expression nuclear miRNA primate-specific splicing Argonaute proteins neuron differentiation |
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| SubjectTerms | Argonaute 2 protein Argonaute proteins Biosynthesis Conserved sequence Homology Insects Localization MicroRNAs miRNA Neural stem cells neuron differentiation Neuroscience nuclear miRNA Post-transcription primate-specific Proteins regulation of gene expression Spliceosomes splicing Transcription factors |
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| Title | miRNA Enriched in Human Neuroblast Nuclei Bind the MAZ Transcription Factor and Their Precursors Contain the MAZ Consensus Motif |
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