Molecular dissection of ALS-linked TDP-43 - involvement of the Gly-rich domain in interaction with G-quadruplex mRNA.

IF 3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
FEBS Letters Pub Date : 2020-07-01 Epub Date: 2020-05-16 DOI:10.1002/1873-3468.13800
Akira Ishiguro, Nobuyuki Kimura, Takashi Noma, Rieko Shimo-Kon, Akira Ishihama, Takahide Kon
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引用次数: 18

Abstract

TDP-43 is the major pathogenic protein of amyotrophic lateral sclerosis (ALS). Previously, we identified that TDP-43 interacts with G-quadruplex (G4)-containing RNA and is involved in their long-distance transport in neurons. For the molecular dissection of the TDP-43 and G4-RNA interaction, we analyzed it here in vitro and in cultured cells using a set of 10 mutant TDP-43 proteins from familial and sporadic ALS patients as well as using the TDP-43 C-terminal Gly-rich domain alone. Our results altogether indicate the involvement of the Gly-rich region of TDP-43 in the initial recognition and binding of G4-RNA, which then induces tight binding of TDP-43 with target RNAs, supposedly in conjunction with its RNA recognition motifs.

als连锁TDP-43的分子解剖-参与Gly-rich结构域与g -四重体mRNA的相互作用。
TDP-43是肌萎缩性侧索硬化症(ALS)的主要致病蛋白。之前,我们发现TDP-43与含有g-四重体(G4)的RNA相互作用,并参与其在神经元中的长距离运输。为了对TDP-43和G4-RNA相互作用进行分子解剖,我们在体外和培养细胞中使用一组来自家族性和散发性ALS患者的10个突变TDP-43蛋白,以及单独使用TDP-43 c端Gly-rich结构域进行分析。我们的研究结果表明,TDP-43富含gly的区域参与了G4-RNA的初始识别和结合,然后诱导TDP-43与靶RNA的紧密结合,可能与其RNA识别基序相结合。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
FEBS Letters
FEBS Letters 生物-生化与分子生物学
CiteScore
6.60
自引率
2.90%
发文量
303
审稿时长
1 months
期刊介绍: FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.
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