globalchange  > 气候变化与战略
DOI: 10.1073/pnas.1814385116
论文题名:
Phosphoregulated FMRP phase separation models activity-dependent translation through bidirectional control of mRNA granule formation
作者: Tsang B.; Arsenault J.; Vernon R.M.; Lin H.; Sonenberg N.; Wang L.-Y.; Bah A.; Forman-Kay J.D.
刊名: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
出版年: 2019
卷: 116, 期:10
起始页码: 4218
结束页码: 4227
语种: 英语
英文关键词: Activity-dependent translation ; Phase separation ; Posttranslational modifications ; RNA granules ; Translational regulation
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
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.
Citation statistics:
资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/163624
Appears in Collections:气候变化与战略

Files in This Item:

There are no files associated with this item.


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, ON M5G 0A4, Canada, Department of Biochemistry and Molecular Biology, State University of New York Upstate Medical University, Syracuse, NY 13210, United States; Forman-Kay, J.D., Program in Molecular Medicine, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada, Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada

Recommended Citation:
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]. Proceedings of the National Academy of Sciences of the United States of America,2019-01-01,116(10)
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Tsang B.]'s Articles
[Arsenault J.]'s Articles
[Vernon R.M.]'s Articles
百度学术
Similar articles in Baidu Scholar
[Tsang B.]'s Articles
[Arsenault J.]'s Articles
[Vernon R.M.]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Tsang B.]‘s Articles
[Arsenault J.]‘s Articles
[Vernon R.M.]‘s Articles
Related Copyright Policies
Null
收藏/分享
所有评论 (0)
暂无评论
 

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.