Top3β is an RNA topoisomerase that works with fragile X syndrome protein to promote synapse formation.
Top3β is an RNA topoisomerase that works with fragile X syndrome protein to promote synapse formation.
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DOI：
10.1038/nn.3479
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发表时间：
2013-09
影响因子：
25
通讯作者：
Wang, Weidong
中科院分区：
文献类型：
--
作者：
Xu, Dongyi;Shen, Weiping;Guo, Rong;Xue, Yutong;Peng, Wei;Sima, Jian;Yang, Jay;Sharov, Alexei;Srikantan, Subramanya;Yang, Jiandong;Fox, David, III;Qian, Yong;Martindale, Jennifer L.;Piao, Yulan;Machamer, James;Joshi, Samit R.;Mohanty, Subhasis;Shaw, Albert C.;Lloyd, Thomas E.;Brown, Grant W.;Ko, Minoru S. H.;Gorospe, Myriam;Zou, Sige;Wang, Weidong
拓扑异构酶是解决DNA拓扑问题的关键，但它们尚未与RNA代谢联系起来。在这里，我们发现人类拓扑异构酶3β (Top3β)是一种RNA拓扑异构酶，其生物化学和遗传上与FMRP相互作用，FMRP是脆性X综合征中缺乏的蛋白质，已知可调节对神经元功能和自闭症重要的mrna的翻译。值得注意的是，FMRP-Top3β相互作用被疾病相关的FMRP突变所消除，这表明Top3β可能有助于精神障碍的发病机制。Top3β结合与精神分裂症和自闭症相关的神经元功能基因编码的多个mrna。其中一个基因ptk2/FAK在Top3β突变果蝇的神经肌肉连接中表达减少。在FMRP突变动物中观察到，Top3β突变体果蝇和小鼠突触形成缺陷。我们的研究结果表明，Top3β作为RNA拓扑异构酶，与FMRP一起促进对神经发育和心理健康至关重要的mrna的表达。
Topoisomerases are crucial to solve DNA topological problems, but they have not been linked to RNA metabolism. Here we show that human topoisomerase 3β (Top3β) is an RNA topoisomerase that biochemically and genetically interacts with FMRP, a protein deficient in Fragile X syndrome and known to regulate translation of mRNAs important for neuronal function and autism. Notably, the FMRP-Top3β interaction is abolished by a disease-associated FMRP mutation, suggesting that Top3β may contribute to pathogenesis of mental disorders. Top3β binds multiple mRNAs encoded by genes with neuronal functions related to schizophrenia and autism. Expression of one such gene, ptk2/FAK, is reduced in neuromuscular junctions of Top3β mutant flies. Synapse formation is defective in Top3β mutant flies and mice, as observed in FMRP mutant animals. Our findings suggest that Top3β acts as an RNA topoisomerase and works with FMRP to promote expression of mRNAs critical for neurodevelopment and mental health.
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影响因子：
16.2
作者：
Iossifov I;Ronemus M;Levy D;Wang Z;Hakker I;Rosenbaum J;Yamrom B;Lee YH;Narzisi G;Leotta A;Kendall J;Grabowska E;Ma B;Marks S;Rodgers L;Stepansky A;Troge J;Andrews P;Bekritsky M;Pradhan K;Ghiban E;Kramer M;Parla J;Demeter R;Fulton LL;Fulton RS;Magrini VJ;Ye K;Darnell JC;Darnell RB;Mardis ER;Wilson RK;Schatz MC;McCombie WR;Wigler M
通讯作者：
Wigler M
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影响因子：
3.5
作者：
Goulet, Isabelle;Boisvenue, Sophie;Mokas, Sophie;Mazroui, Rachid;Cote, Jocelyn
通讯作者：
Cote, Jocelyn
影响因子：
25
作者：
通讯作者：
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影响因子：
16.8
作者：
通讯作者：
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影响因子：
64.5
作者：
Kwan KY;Lam MM;Johnson MB;Dube U;Shim S;Rašin MR;Sousa AM;Fertuzinhos S;Chen JG;Arellano JI;Chan DW;Pletikos M;Vasung L;Rowitch DH;Huang EJ;Schwartz ML;Willemsen R;Oostra BA;Rakic P;Heffer M;Kostović I;Judaš M;Sestan N
通讯作者：
Sestan N