Systematic genetic interaction screens uncover cell polarity regulators and functional redundancy.
Systematic genetic interaction screens uncover cell polarity regulators and functional redundancy.
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DOI：
10.1038/ncb2639
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发表时间：
2013-01
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
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作者：
尽管单基因功能丧失分析可以识别特定过程的组成部分，但由于生物系统的稳健性，重要的分子会被遗漏。在这里，我们表明，大规模RNAi筛选与功能相关突变体的抑制相互作用极大地扩展了已知在共享过程中起作用的基因库，并揭示了新的功能关系层。我们对 17 个线虫细胞极性突变体进行了 RNAi 筛选，产生了后生动物中最全面的极性网络，连接了 184 个基因。其中，72% 以前与细胞极性无关，80% 具有人类同源物。我们通过实验证实了网络预测的功能作用，并通过生物物理分析八个肌球蛋白调节剂进行了表征。此外，我们发现两个未知极性基因之间的功能冗余。针对其他生物过程的类似系统遗传相互作用筛选将有助于揭示相关基因的库存及其相互作用模式。
Although single gene loss of function analyses can identify components of particular processes, important molecules are missed due to the robustness of biological systems. Here we show that large scale RNAi screening for suppression interactions with functionally related mutants greatly expands the repertoire of genes known to act in a shared process and reveals a new layer of functional relationships. We performed RNAi screens for 17 C. elegans cell polarity mutants, generating the most comprehensive polarity network in a metazoan, connecting 184 genes. Of these, 72% were not previously linked to cell polarity and 80% have human homologs. We experimentally confirmed functional roles predicted by the network and characterised through biophysical analyses eight myosin regulators. In addition, we discovered functional redundancy between two unknown polarity genes. Similar systematic genetic interaction screens for other biological processes will help uncover the inventory of relevant genes and their patterns of interactions.
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影响因子：
64.8
作者：
Cowan, CR;Hyman, AA
通讯作者：
Hyman, AA
影响因子：
--
作者：
Dong, Yan;Bogdanova, Aliona;Ahringer, Julie
通讯作者：
Ahringer, Julie
影响因子：
64.8
作者：
Guo, S;Kemphues, KJ
通讯作者：
Kemphues, KJ
影响因子：
4.6
作者：
Bergmann, DC;Lee, M;Wood, WB
通讯作者：
Wood, WB
DOI：
10.1126/science.1180823
发表时间：
2010-01-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Costanzo M;Baryshnikova A;Bellay J;Kim Y;Spear ED;Sevier CS;Ding H;Koh JL;Toufighi K;Mostafavi S;Prinz J;St Onge RP;VanderSluis B;Makhnevych T;Vizeacoumar FJ;Alizadeh S;Bahr S;Brost RL;Chen Y;Cokol M;Deshpande R;Li Z;Lin ZY;Liang W;Marback M;Paw J;San Luis BJ;Shuteriqi E;Tong AH;van Dyk N;Wallace IM;Whitney JA;Weirauch MT;Zhong G;Zhu H;Houry WA;Brudno M;Ragibizadeh S;Papp B;Pál C;Roth FP;Giaever G;Nislow C;Troyanskaya OG;Bussey H;Bader GD;Gingras AC;Morris QD;Kim PM;Kaiser CA;Myers CL;Andrews BJ;Boone C
通讯作者：
Boone C