气候变化领域集成服务门户(CCPortal): Phosphoregulated FMRP phase separation models activity-dependent translation through bidirectional control of mRNA granule formation

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DOI	10.1073/pnas.1814385116
	Phosphoregulated FMRP phase separation models activity-dependent translation through bidirectional control of mRNA granule formation
	Tsang B.; Arsenault J.; Vernon R.M.; Lin H.; Sonenberg N.; Wang L.-Y.; Bah A.; Forman-Kay J.D.
发表日期	2019
ISSN	0027-8424
起始页码	4218
结束页码	4227
卷号	116 期号:10
英文摘要	Activity-dependent translation requires the transport of mRNAs within membraneless protein assemblies known as neuronal granules from the cell body toward synaptic regions. Translation of mRNA is inhibited in these granules during transport but quickly activated in response to neuronal stimuli at the synapse. This raises an important question: how does synaptic activity trigger translation of once-silenced mRNAs? Here, we demonstrate a strong connection between phase separation, the process underlying the formation of many different types of cellular granules, and in vitro inhibition of translation. By using the Fragile X Mental Retardation Protein (FMRP), an abundant neuronal granule component and translational repressor, we show that FMRP phase separates in vitro with RNA into liquid droplets mediated by its C-terminal low-complexity disordered region (i.e., FMRP LCR ). FMRP LCR posttranslational modifications by phosphorylation and methylation have opposing effects on in vitro translational regulation, which corroborates well with their critical concentrations for phase separation. Our results, combined with bioinformatics evidence, are supportive of phase separation as a general mechanism controlling activity-dependent translation. © 2019 National Academy of Sciences. All Rights Reserved.
英文关键词	Activity-dependent translation; Phase separation; Posttranslational modifications; RNA granules; Translational regulation
语种	英语
scopus关键词	fragile X mental retardation protein; messenger RNA; fragile X mental retardation protein; messenger RNA; microRNA; animal cell; Article; carboxy terminal sequence; concentration (parameter); controlled study; fluorescence microscopy; in vitro study; nonhuman; phase separation; priority journal; protein expression; protein phosphorylation; protein purification; RNA translation; animal; cell granule; CHO cell line; Cricetulus; genetic transcription; metabolism; methylation; nerve cell; phosphorylation; protein processing; synapse; Animals; CHO Cells; Cricetulus; Cytoplasmic Granules; Fragile X Mental Retardation Protein; Methylation; MicroRNAs; Neurons; Phosphorylation; Protein Processing, Post-Translational; RNA, Messenger; Synapses; Transcription, Genetic
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160431
作者单位	Tsang, B., Program in Molecular Medicine, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada, Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Arsenault, J., Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada, Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Vernon, R.M., Program in Molecular Medicine, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Lin, H., Program in Molecular Medicine, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Sonenberg, N., Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada, Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Wang, L.-Y., Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada, Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Bah, A., Program in Molecular Medicine, Hospital for Sick Children, Toronto...
推荐引用方式 GB/T 7714	Tsang B.,Arsenault J.,Vernon R.M.,et al. Phosphoregulated FMRP phase separation models activity-dependent translation through bidirectional control of mRNA granule formation[J],2019,116(10).
APA	Tsang B..,Arsenault J..,Vernon R.M..,Lin H..,Sonenberg N..,...&Forman-Kay J.D..(2019).Phosphoregulated FMRP phase separation models activity-dependent translation through bidirectional control of mRNA granule formation.Proceedings of the National Academy of Sciences of the United States of America,116(10).
MLA	Tsang B.,et al."Phosphoregulated FMRP phase separation models activity-dependent translation through bidirectional control of mRNA granule formation".Proceedings of the National Academy of Sciences of the United States of America 116.10(2019).