Mov10 suppresses retroelements and regulates neuronal development and function in the developing brain
Abstract Background Moloney leukemia virus 10 (Mov10) is an RNA helicase that mediates access of the RNA-induced silencing complex to messenger RNAs (mRNAs). Until now, its role as an RNA helicase and as a regulator of retrotransposons has been characterized exclusively in cell lines. We investigate...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | BMC Biology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12915-017-0387-1 |
| _version_ | 1818383443772309504 |
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| author | Geena Skariah Joseph Seimetz Miles Norsworthy Monica C. Lannom Phillip J. Kenny Mohamed Elrakhawy Craig Forsthoefel Jenny Drnevich Auinash Kalsotra Stephanie Ceman |
| author_facet | Geena Skariah Joseph Seimetz Miles Norsworthy Monica C. Lannom Phillip J. Kenny Mohamed Elrakhawy Craig Forsthoefel Jenny Drnevich Auinash Kalsotra Stephanie Ceman |
| author_sort | Geena Skariah |
| collection | DOAJ |
| description | Abstract Background Moloney leukemia virus 10 (Mov10) is an RNA helicase that mediates access of the RNA-induced silencing complex to messenger RNAs (mRNAs). Until now, its role as an RNA helicase and as a regulator of retrotransposons has been characterized exclusively in cell lines. We investigated the role of Mov10 in the mouse brain by examining its expression over development and attempting to create a Mov10 knockout mouse. Loss of both Mov10 copies led to early embryonic lethality. Results Mov10 was significantly elevated in postnatal murine brain, where it bound retroelement RNAs and mRNAs. Mov10 suppressed retroelements in the nucleus by directly inhibiting complementary DNA synthesis, while cytosolic Mov10 regulated cytoskeletal mRNAs to influence neurite outgrowth. We verified this important function by observing reduced dendritic arborization in hippocampal neurons from the Mov10 heterozygote mouse and shortened neurites in the Mov10 knockout Neuro2A cells. Knockdown of Fmrp also resulted in shortened neurites. Mov10, Fmrp, and Ago2 bound a common set of mRNAs in the brain. Reduced Mov10 in murine brain resulted in anxiety and increased activity in a novel environment, supporting its important role in the development of normal brain circuitry. Conclusions Mov10 is essential for normal neuronal development and brain function. Mov10 preferentially binds RNAs involved in actin binding, neuronal projection, and cytoskeleton. This is a completely new and critically important function for Mov10 in neuronal development and establishes a precedent for Mov10 being an important candidate in neurological disorders that have underlying cytoarchitectural causes like autism and Alzheimer’s disease. |
| first_indexed | 2024-12-14T03:06:27Z |
| format | Article |
| id | doaj.art-2378c5d379f844ebb71dd0031d7ee75d |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-12-14T03:06:27Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-2378c5d379f844ebb71dd0031d7ee75d2022-12-21T23:19:23ZengBMCBMC Biology1741-70072017-06-0115111910.1186/s12915-017-0387-1Mov10 suppresses retroelements and regulates neuronal development and function in the developing brainGeena Skariah0Joseph Seimetz1Miles Norsworthy2Monica C. Lannom3Phillip J. Kenny4Mohamed Elrakhawy5Craig Forsthoefel6Jenny Drnevich7Auinash Kalsotra8Stephanie Ceman9Neuroscience Program, University of Illinois-Urbana ChampaignBiochemistry, University of Illinois-Urbana ChampaignCell and Developmental Biology, University of Illinois-Urbana ChampaignCell and Developmental Biology, University of Illinois-Urbana ChampaignCell and Developmental Biology, University of Illinois-Urbana ChampaignCell and Developmental Biology, University of Illinois-Urbana ChampaignCollege of Medicine, University of Illinois-Urbana ChampaignHigh-Performance Biological Computing, Roy J. Carver Biotechnology Center, University of Illinois-Urbana ChampaignBiochemistry, University of Illinois-Urbana ChampaignNeuroscience Program, University of Illinois-Urbana ChampaignAbstract Background Moloney leukemia virus 10 (Mov10) is an RNA helicase that mediates access of the RNA-induced silencing complex to messenger RNAs (mRNAs). Until now, its role as an RNA helicase and as a regulator of retrotransposons has been characterized exclusively in cell lines. We investigated the role of Mov10 in the mouse brain by examining its expression over development and attempting to create a Mov10 knockout mouse. Loss of both Mov10 copies led to early embryonic lethality. Results Mov10 was significantly elevated in postnatal murine brain, where it bound retroelement RNAs and mRNAs. Mov10 suppressed retroelements in the nucleus by directly inhibiting complementary DNA synthesis, while cytosolic Mov10 regulated cytoskeletal mRNAs to influence neurite outgrowth. We verified this important function by observing reduced dendritic arborization in hippocampal neurons from the Mov10 heterozygote mouse and shortened neurites in the Mov10 knockout Neuro2A cells. Knockdown of Fmrp also resulted in shortened neurites. Mov10, Fmrp, and Ago2 bound a common set of mRNAs in the brain. Reduced Mov10 in murine brain resulted in anxiety and increased activity in a novel environment, supporting its important role in the development of normal brain circuitry. Conclusions Mov10 is essential for normal neuronal development and brain function. Mov10 preferentially binds RNAs involved in actin binding, neuronal projection, and cytoskeleton. This is a completely new and critically important function for Mov10 in neuronal development and establishes a precedent for Mov10 being an important candidate in neurological disorders that have underlying cytoarchitectural causes like autism and Alzheimer’s disease.http://link.springer.com/article/10.1186/s12915-017-0387-1RNA helicaseRISCBrainNeurite outgrowthEmbryonic developmentMov10 |
| spellingShingle | Geena Skariah Joseph Seimetz Miles Norsworthy Monica C. Lannom Phillip J. Kenny Mohamed Elrakhawy Craig Forsthoefel Jenny Drnevich Auinash Kalsotra Stephanie Ceman Mov10 suppresses retroelements and regulates neuronal development and function in the developing brain BMC Biology RNA helicase RISC Brain Neurite outgrowth Embryonic development Mov10 |
| title | Mov10 suppresses retroelements and regulates neuronal development and function in the developing brain |
| title_full | Mov10 suppresses retroelements and regulates neuronal development and function in the developing brain |
| title_fullStr | Mov10 suppresses retroelements and regulates neuronal development and function in the developing brain |
| title_full_unstemmed | Mov10 suppresses retroelements and regulates neuronal development and function in the developing brain |
| title_short | Mov10 suppresses retroelements and regulates neuronal development and function in the developing brain |
| title_sort | mov10 suppresses retroelements and regulates neuronal development and function in the developing brain |
| topic | RNA helicase RISC Brain Neurite outgrowth Embryonic development Mov10 |
| url | http://link.springer.com/article/10.1186/s12915-017-0387-1 |
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