Systematic analysis of atx-2 suppressors reveals a novel regulator of PAR-5/14-3-3sigma function during mitosis in Caenorhabditis elegans
Systematic analysis of atx-2 suppressors reveals a novel regulator of PAR-5/14-3-3sigma function during mitosis in Caenorhabditis elegans
复制标题
atx-2 抑制剂的系统分析揭示了秀丽隐杆线虫有丝分裂期间 PAR-5/14-3-3sigma 功能的新型调节剂
DOI：
10.1101/173856
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Megan M. Gnazzo, Alex R.
中科院分区：
文献类型：
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作者：
Megan M. Gnazzo, Alex R.
RNA调控在有丝分裂中起关键作用，但其机制尚不清楚。我们的实验室最近发现，保守的rna结合蛋白（RBP） ATX-2通过一个保守的翻译调节因子PAR-5/14-3-3sigma调节ZEN-4在纺锤体中间区的靶向，从而调节细胞分裂。虽然ATX-2和PAR-5的共同耗竭恢复了ZEN-4对纺锤体中间区的靶向，但它并没有挽救细胞分裂。为了确定可能与ATX-2协同作用以调节细胞分裂的因素，我们进行了两部分，候选RNAi抑制因子和视觉筛选，以确定对细胞分裂重要的因素，并介导ATX-2靶向到中心体和纺锤体中间区。利用这种方法，我们鉴定了10个抑制在atx-2突变胚胎中观察到的胚胎致死缺陷的基因。这十个基因，包括act-2、cgh-1、cki-1、hum-6、par-2、rnp-4、vab-3、vhl-1、vps-24和wve-1，都有一定的调控RNA或细胞周期的作用。这些基因中的5个（cgh-1,cki-1,vab-3,vhl-1,vps-24）在耗尽时不能将ATX-2靶向到中心体和中间区。theatx-2表型最强的抑制因子是DEAD-box RNA解旋酶CGH-1/DDX6，它与细胞分裂、RNA加工和翻译以及神经元功能有关。CGH-1的缺失修复了细胞分裂缺陷，并恢复了ZEN-4在纺锤体中部的定位。ATX-2和CGH-1定位于中心体和纺锤体中间区是相互需要的。我们的研究结果提供了第一个功能证据，证明CGH-1/DDX6在有丝分裂期间通过PAR-5/14-3-3sigma调节ATX-2功能，将ZEN-4靶向到纺锤体中间区。我们认为RNA机制是完成细胞分裂所必需的。
RNA regulation plays a critical role in mitosis, yet the mechanisms remain unclear. Our lab recently identified that the conserved RNA-Binding Protein (RBP), ATX-2, regulates cytokinesis by regulating the targeting of ZEN-4 to the spindle midzone through a conserved translation regulator, PAR-5/14-3-3sigma . While co-depletion of ATX-2 and PAR-5 restored ZEN-4 targeting to the spindle midzone, it did not rescue cell division. To identify factors that may work in concert with ATX-2 to regulate cell division, we conducted a two-part, candidate RNAi suppressor and visual screen to identify factors that are important for cell division and also mediate the targeting of ATX-2 to the centrosomes and the spindle midzone. Using this approach, we identified ten genes that suppress the embryonic lethality defect observed inatx-2mutant embryos. These ten genes, includingact-2,cgh-1,cki-1,hum-6,par-2,rnp-4,vab-3,vhl-1,vps-24, andwve-1, all have some role regulating RNA or the cell cycle. Five of these genes (cgh-1,cki-1,vab-3,vhl-1,vps-24) fail to target ATX-2 to the centrosomes and midzone when depleted. The strongest suppressor of theatx-2phenotype is the DEAD-box RNA helicase CGH-1/DDX6, which has been implicated in cell division, RNA processing and translation, and neuronal function. Loss of CGH-1 rescued the cytokinesis defect and also restored ZEN-4 localization to the spindle midzone. ATX-2 and CGH-1 are mutually required for their localization to centrosomes and the spindle midzone. Our findings provide the first functional evidence that CGH-1/DDX6 regulates ATX-2 function during mitosis to target ZEN-4 to the spindle midzone via PAR-5/14-3-3sigma. We suggest that RNA machinery is necessary for the completion of cytokinesis.
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影响因子：
4.6
作者：
C. A. Shelton;B. Bowerman
通讯作者：
C. A. Shelton;B. Bowerman
成年人类海马神经发生的动力学。
影响因子：
64.5
作者：
Spalding KL;Bergmann O;Alkass K;Bernard S;Salehpour M;Huttner HB;Boström E;Westerlund I;Vial C;Buchholz BA;Possnert G;Mash DC;Druid H;Frisén J
通讯作者：
Frisén J
裂殖酵母通用翻译因子揭示了蛋白质合成和细胞周期控制之间的联系。
影响因子：
4
作者：
Beáta Grallert;S. Kearsey;Michael Lenhard;Michael Lenhard;C. R. Carlson;P. Nurse;Erik Boye;Karim Labib
通讯作者：
Karim Labib
影响因子：
14.9
作者：
Nicklas S;Okawa S;Hillje AL;González-Cano L;Del Sol A;Schwamborn JC
通讯作者：
Schwamborn JC
影响因子：
21.3
作者：
通讯作者：
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