期刊
ELIFE
卷 10, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.67605
关键词
RNA; RNA-binding proteins; neurodegenerative diseases; Human
类别
资金
- Genopole SATURNE 2018-SABNP
- Association pour la recherche sur la SLA (ARSLA) [eOTP 19SATSAB02]
- Region Ile-de-France SESAME [15013102]
- Genopole
- University Evry UEVE FRR-Action 2
The study reveals that the tandem RNA recognition motifs of TDP-43 cooperatively bind to long GU-repeats, maintaining its solubility. The cooperative binding of TDP-43 to mRNA is crucial for preserving its solubility in the nucleus and miscibility in cytoplasmic stress granules.
TDP-43 is a nuclear RNA-binding protein that forms neuronal cytoplasmic inclusions in two major neurodegenerative diseases, ALS and FTLD. While the self-assembly of TDP-43 by its structured N-terminal and intrinsically disordered C-terminal domains has been widely studied, the mechanism by which mRNA preserves TDP-43 solubility in the nucleus has not been addressed. Here, we demonstrate that tandem RNA recognition motifs of TDP-43 bind to long GU-repeats in a cooperative manner through intermolecular interactions. Moreover, using mutants whose cooperativity is impaired, we found that the cooperative binding of TDP-43 to mRNA may be critical to maintain the solubility of TDP-43 in the nucleus and the miscibility of TDP-43 in cytoplasmic stress granules. We anticipate that the knowledge of a higher order assembly of TDP-43 on mRNA may clarify its role in intron processing and provide a means of interfering with the cytoplasmic aggregation of TDP-43.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据