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DOI | 10.1038/ncomms14557 |
Phase separation-deficient TDP43 remains functional in splicing | |
Schmidt, Hermann Broder1; Barreau, Ariana1; Rohatgi, Rajat1,2 | |
2019-10-25 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Intrinsically disordered regions (IDRs) are often fast-evolving protein domains of low sequence complexity that can drive phase transitions and are commonly found in many proteins associated with neurodegenerative diseases, including the RNA processing factor TDP43. Yet, how phase separation contributes to the physiological functions of TDP43 in cells remains enigmatic. Here, we combine systematic mutagenesis guided by evolutionary sequence analysis with a live-cell reporter assay of TDP43 phase dynamics to identify regularly-spaced hydrophobic motifs separated by flexible, hydrophilic segments in the IDR as a key determinant of TDP43 phase properties. This heuristic framework allows customization of the material properties of TDP43 condensates to determine effects on splicing function. Remarkably, even a mutant that fails to phase-separate at physiological concentrations can still efficiently mediate the splicing of a quantitative, single-cell splicing reporter and endogenous targets. This suggests that the ability of TDP43 to phase-separate is not essential for its splicing function. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000492835100028 |
WOS关键词 | FRONTOTEMPORAL LOBAR DEGENERATION ; LOW-COMPLEXITY DOMAINS ; TDP-43 MUTATIONS ; LIQUID DROPLETS ; NUCLEAR-BODIES ; PROTEIN ; AGGREGATION ; SCLEROSIS ; REGION ; COACERVATION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203238 |
专题 | 资源环境科学 |
作者单位 | 1.Stanford Sch Med, Dept Biochem, Stanford, CA 94305 USA; 2.Stanford Sch Med, Dept Med, Stanford, CA 94305 USA |
推荐引用方式 GB/T 7714 | Schmidt, Hermann Broder,Barreau, Ariana,Rohatgi, Rajat. Phase separation-deficient TDP43 remains functional in splicing[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Schmidt, Hermann Broder,Barreau, Ariana,&Rohatgi, Rajat.(2019).Phase separation-deficient TDP43 remains functional in splicing.NATURE COMMUNICATIONS,10. |
MLA | Schmidt, Hermann Broder,et al."Phase separation-deficient TDP43 remains functional in splicing".NATURE COMMUNICATIONS 10(2019). |
条目包含的文件 | 条目无相关文件。 |
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