Biogenesis and function of microRNA miR-124
MicroRNAs are 19-25 nucleotides long non-coding RNAs that base-pair with cognate mRNA targets and regulate their translation and/or stability. Different miRNAs have been implicated in the regulation of essential biological processes like differentiation, proliferation and apoptosis. miR-124 is a con...
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| Format: | Thesis |
| Language: | English |
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2013
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| Online Access: | https://hdl.handle.net/10356/54900 |
| _version_ | 1826125006028931072 |
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| author | Manish Muhuri |
| author2 | Eugene Makeyev |
| author_facet | Eugene Makeyev Manish Muhuri |
| author_sort | Manish Muhuri |
| collection | NTU |
| description | MicroRNAs are 19-25 nucleotides long non-coding RNAs that base-pair with cognate mRNA targets and regulate their translation and/or stability. Different miRNAs have been implicated in the regulation of essential biological processes like differentiation, proliferation and apoptosis. miR-124 is a conserved, abundantly expressed neuron-specific microRNA that has been previously shown to contribute to neurogenesis by targeting several important transcripts. miR-124 is expressed in neurons, but not glial cells, and the levels of miR-124 increase over time in the developing nervous system (NS). Similar to a few other vertebrate microRNAs, mature miR-124 is encoded by three distinct non-allelic genes in human and mouse genome. To understand biological significance of this genetic redundancy, we examined spatio-temporal expression patterns of the three genes in developing mouse embryo. Two miR-124 genes were expressed at detectable levels in both neural stem cells (NSCs) and post-mitotic neurons, whereas the third gene was expressed exclusively in neurons. Notably, knocking out the neuron-specific miR-124 gene in mouse led, in addition to other interesting phenotypes, to over-proliferation of the neuroepithelial layer containing embryonic NSCs which are positive for certain proliferation markers. These data suggest that one of the functions of the multiple miR-124 genes in mouse could be limiting the NSC proliferation potential and ensuring temporal precision of neuronal differentiation.
In a separate line of experiments, we have investigated post-transcriptional mechanisms underlying miR-124 biogenesis. Interestingly, processing of miR-124 from the pri-miR-124-2 precursor requires the presence of a functional intron, consistent with the native genetic structure of this precursor. We show that the unusually strong dependence of 124-2 on the splicing reaction is due to the presence of a tunable cis-regulatory element that induces rapid degradation of the pri-miR-124-2 precursor unless this element is positioned within a spliceable intron. These data uncover a novel post-transcriptional mechanism regulating miRNA expression which could also possibly modulate the mature miRNA output of the 124-2 gene in vivo. |
| first_indexed | 2024-10-01T06:29:40Z |
| format | Thesis |
| id | ntu-10356/54900 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:29:40Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | ntu-10356/549002023-02-28T18:44:22Z Biogenesis and function of microRNA miR-124 Manish Muhuri Eugene Makeyev School of Biological Sciences DRNTU::Science::Biological sciences::Molecular biology MicroRNAs are 19-25 nucleotides long non-coding RNAs that base-pair with cognate mRNA targets and regulate their translation and/or stability. Different miRNAs have been implicated in the regulation of essential biological processes like differentiation, proliferation and apoptosis. miR-124 is a conserved, abundantly expressed neuron-specific microRNA that has been previously shown to contribute to neurogenesis by targeting several important transcripts. miR-124 is expressed in neurons, but not glial cells, and the levels of miR-124 increase over time in the developing nervous system (NS). Similar to a few other vertebrate microRNAs, mature miR-124 is encoded by three distinct non-allelic genes in human and mouse genome. To understand biological significance of this genetic redundancy, we examined spatio-temporal expression patterns of the three genes in developing mouse embryo. Two miR-124 genes were expressed at detectable levels in both neural stem cells (NSCs) and post-mitotic neurons, whereas the third gene was expressed exclusively in neurons. Notably, knocking out the neuron-specific miR-124 gene in mouse led, in addition to other interesting phenotypes, to over-proliferation of the neuroepithelial layer containing embryonic NSCs which are positive for certain proliferation markers. These data suggest that one of the functions of the multiple miR-124 genes in mouse could be limiting the NSC proliferation potential and ensuring temporal precision of neuronal differentiation. In a separate line of experiments, we have investigated post-transcriptional mechanisms underlying miR-124 biogenesis. Interestingly, processing of miR-124 from the pri-miR-124-2 precursor requires the presence of a functional intron, consistent with the native genetic structure of this precursor. We show that the unusually strong dependence of 124-2 on the splicing reaction is due to the presence of a tunable cis-regulatory element that induces rapid degradation of the pri-miR-124-2 precursor unless this element is positioned within a spliceable intron. These data uncover a novel post-transcriptional mechanism regulating miRNA expression which could also possibly modulate the mature miRNA output of the 124-2 gene in vivo. DOCTOR OF PHILOSOPHY (SBS) 2013-10-22T08:46:17Z 2013-10-22T08:46:17Z 2013 2013 Thesis Manish Muhuri. (2013). Biogenesis and function of microRNA miR-124. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/54900 10.32657/10356/54900 en 229 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences::Molecular biology Manish Muhuri Biogenesis and function of microRNA miR-124 |
| title | Biogenesis and function of microRNA miR-124 |
| title_full | Biogenesis and function of microRNA miR-124 |
| title_fullStr | Biogenesis and function of microRNA miR-124 |
| title_full_unstemmed | Biogenesis and function of microRNA miR-124 |
| title_short | Biogenesis and function of microRNA miR-124 |
| title_sort | biogenesis and function of microrna mir 124 |
| topic | DRNTU::Science::Biological sciences::Molecular biology |
| url | https://hdl.handle.net/10356/54900 |
| work_keys_str_mv | AT manishmuhuri biogenesisandfunctionofmicrornamir124 |