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Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
Published on: April 22, 2017
RMRP mediates neuroprotection as a downstream effector of RBM3 in human neuroblastoma SH-SY5Y cells
Shuangping Ma1,2, Xianting Liu3,4, Yiming Xie5
1Institutes of Health Central Plain, Henan Medical University, Xinxiang, 453003, Henan, China. 211042@xxmu.edu.cn.
The RNA component of mitochondrial RNA processing endoribonuclease (RMRP) mediates neuroprotection by enhancing global protein synthesis. This study reveals RMRP as a key effector of RBM3, offering a potential therapeutic target for Parkinson's disease.
Area of Science:
- Molecular Biology
- Neuroscience
- RNA Biology
Background:
- Long non-coding RNA (lncRNA) RMRP is involved in ribosome biogenesis and has emerging roles in neurodegeneration.
- The precise molecular mechanisms of RMRP-mediated neuroprotection are not fully understood.
- RNA-binding protein RBM3 is known for its neuroprotective effects.
Purpose of the Study:
- To investigate the regulatory relationship between RBM3 and RMRP.
- To elucidate the functional role of RMRP in RBM3-mediated neuroprotection in Parkinson's disease models.
- To explore RMRP's impact on global protein synthesis.
Main Methods:
- SH-SY5Y neural cells were used to study RMRP expression regulation by RBM3.
- RNA Immunoprecipitation (RIP) assays were performed to confirm RMRP-RBM3 interaction.
- Neurotoxicity assays using rotenone (ROT) and MPP+ were conducted to assess RMRP's protective effects.
- Eukaryotic elongation factor 2 (eEF2) activity and puromycin incorporation assays were used to measure global protein synthesis.
Main Results:
- RBM3 overexpression upregulated RMRP transcription, while RBM3 knockdown decreased RMRP expression.
- RMRP overexpression significantly attenuated rotenone- and MPP+-induced cytotoxicity in SH-SY5Y cells.
- RMRP overexpression enhanced eEF2 activity and global protein synthesis, validating its role as a mediator of RBM3's neuroprotective function.
Conclusions:
- RMRP is transcriptionally regulated by RBM3.
- RMRP acts as a novel effector of RBM3, stimulating global protein synthesis and conferring neuroprotection in neural cells.
- RMRP represents a potential therapeutic target for Parkinson's disease.
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