LncRNA Litchi is a regulator for harmonizing maturity and resilient functionality in spinal motor neurons
Summary: Long noncoding RNAs (lncRNAs) play pivotal roles in modulating gene expression during development and disease. Despite their high expression in the central nervous system (CNS), understanding the precise physiological functions of CNS-associated lncRNAs has been challenging, largely due to...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-03-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224004280 |
| _version_ | 1827342057956442112 |
|---|---|
| author | Ho-Chiang Hsu Sheng-Ping Hsu Fang-Yu Hsu Mien Chang Jun-An Chen |
| author_facet | Ho-Chiang Hsu Sheng-Ping Hsu Fang-Yu Hsu Mien Chang Jun-An Chen |
| author_sort | Ho-Chiang Hsu |
| collection | DOAJ |
| description | Summary: Long noncoding RNAs (lncRNAs) play pivotal roles in modulating gene expression during development and disease. Despite their high expression in the central nervous system (CNS), understanding the precise physiological functions of CNS-associated lncRNAs has been challenging, largely due to the in vitro-centric nature of studies in this field. Here, utilizing mouse embryonic stem cell (ESC)-derived motor neurons (MNs), we identified an unexplored MN-specific lncRNA, Litchi (Long Intergenic RNAs in Chat Intron). By employing an ''exon-only'' deletion strategy in ESCs and a mouse model, we reveal that Litchi deletion profoundly impacts MN dendritic complexity, axonal growth, and altered action potential patterns. Mechanistically, voltage-gated channels and neurite growth-related genes exhibited heightened sensitivity to Litchi deletion. Our Litchi-knockout mouse model displayed compromised motor behaviors and reduced muscle strength, highlighting Litchi’s critical role in motor function. This study unveils an underappreciated function of lncRNAs in orchestrating MN maturation and maintaining robust electrophysiological properties. |
| first_indexed | 2024-03-07T22:00:00Z |
| format | Article |
| id | doaj.art-5ba128b0932a4fbbb8e2614925283f42 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-07T22:00:00Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-5ba128b0932a4fbbb8e2614925283f422024-02-24T04:55:17ZengElsevieriScience2589-00422024-03-01273109207LncRNA Litchi is a regulator for harmonizing maturity and resilient functionality in spinal motor neuronsHo-Chiang Hsu0Sheng-Ping Hsu1Fang-Yu Hsu2Mien Chang3Jun-An Chen4Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan; Taiwan International Graduate Program in Interdisciplinary Neuroscience, National Cheng Kung University and Academia Sinica, Taipei, TaiwanInstitute of Molecular Biology, Academia Sinica, Taipei 11529, TaiwanInstitute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan; Genome and Systems Biology Degree Program, Academia Sinica and National Taiwan University, Taipei 10617, TaiwanInstitute of Molecular Biology, Academia Sinica, Taipei 11529, TaiwanInstitute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan; Taiwan International Graduate Program in Interdisciplinary Neuroscience, National Cheng Kung University and Academia Sinica, Taipei, Taiwan; Neuroscience Program of Academia Sinica, Academia Sinica, Taipei, Taiwan; Genome and Systems Biology Degree Program, Academia Sinica and National Taiwan University, Taipei 10617, Taiwan; Corresponding authorSummary: Long noncoding RNAs (lncRNAs) play pivotal roles in modulating gene expression during development and disease. Despite their high expression in the central nervous system (CNS), understanding the precise physiological functions of CNS-associated lncRNAs has been challenging, largely due to the in vitro-centric nature of studies in this field. Here, utilizing mouse embryonic stem cell (ESC)-derived motor neurons (MNs), we identified an unexplored MN-specific lncRNA, Litchi (Long Intergenic RNAs in Chat Intron). By employing an ''exon-only'' deletion strategy in ESCs and a mouse model, we reveal that Litchi deletion profoundly impacts MN dendritic complexity, axonal growth, and altered action potential patterns. Mechanistically, voltage-gated channels and neurite growth-related genes exhibited heightened sensitivity to Litchi deletion. Our Litchi-knockout mouse model displayed compromised motor behaviors and reduced muscle strength, highlighting Litchi’s critical role in motor function. This study unveils an underappreciated function of lncRNAs in orchestrating MN maturation and maintaining robust electrophysiological properties.http://www.sciencedirect.com/science/article/pii/S2589004224004280NeuroscienceOmics |
| spellingShingle | Ho-Chiang Hsu Sheng-Ping Hsu Fang-Yu Hsu Mien Chang Jun-An Chen LncRNA Litchi is a regulator for harmonizing maturity and resilient functionality in spinal motor neurons iScience Neuroscience Omics |
| title | LncRNA Litchi is a regulator for harmonizing maturity and resilient functionality in spinal motor neurons |
| title_full | LncRNA Litchi is a regulator for harmonizing maturity and resilient functionality in spinal motor neurons |
| title_fullStr | LncRNA Litchi is a regulator for harmonizing maturity and resilient functionality in spinal motor neurons |
| title_full_unstemmed | LncRNA Litchi is a regulator for harmonizing maturity and resilient functionality in spinal motor neurons |
| title_short | LncRNA Litchi is a regulator for harmonizing maturity and resilient functionality in spinal motor neurons |
| title_sort | lncrna litchi is a regulator for harmonizing maturity and resilient functionality in spinal motor neurons |
| topic | Neuroscience Omics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224004280 |
| work_keys_str_mv | AT hochianghsu lncrnalitchiisaregulatorforharmonizingmaturityandresilientfunctionalityinspinalmotorneurons AT shengpinghsu lncrnalitchiisaregulatorforharmonizingmaturityandresilientfunctionalityinspinalmotorneurons AT fangyuhsu lncrnalitchiisaregulatorforharmonizingmaturityandresilientfunctionalityinspinalmotorneurons AT mienchang lncrnalitchiisaregulatorforharmonizingmaturityandresilientfunctionalityinspinalmotorneurons AT junanchen lncrnalitchiisaregulatorforharmonizingmaturityandresilientfunctionalityinspinalmotorneurons |