Revealing Functional Crosstalk between Distinct Bioprocesses through Reciprocal Functional Tests of Genetically Interacting Genes
Revealing Functional Crosstalk between Distinct Bioprocesses through Reciprocal Functional Tests of Genetically Interacting Genes
复制标题
通过遗传相互作用基因的相互功能测试揭示不同生物过程之间的功能串扰
DOI：
10.1016/j.celrep.2019.10.076
复制
发表时间：
2019-11-26
期刊：
影响因子：
8.8
通讯作者：
Xia, Tian
中科院分区：
文献类型：
--
作者：
Chen, Dan;Xu, Wei;Xia, Tian
为了系统地探索调节后生动物生物过程之间功能串扰的基因，我们应用比较遗传相互作用(GI)定位技术在酿酒酵母和秀丽线虫中构建了一个由178个秀丽线虫GI组成的生物过程间网络。GI网络跨越六个已注释的生物过程，包括衰老、细胞内运输、基于微管的过程、细胞质分裂、脂代谢过程和解剖结构发展。通过提出相互作用基因对的“互易功能测试”策略，我们发现了一组在不同生物过程之间调节串扰的基因。尤其是，我们发现核糖体S6Kinase/RSKS-1，以前被描述为mTOR(雷帕霉素的机械靶标)效应，作为DAF-2内体循环运输的调节因子，追踪内吞再循环和衰老过程之间的功能相关性。总之，我们的结果为在几乎没有先验知识的情况下识别调节生物过程之间串扰的基因和途径提供了一种替代和有效的策略。
To systematically explore the genes mediating functional crosstalk between metazoan biological processes, we apply comparative genetic interaction (GI) mapping in Saccharomyces cerevisiae and Caenorhabditis elegans to generate an inter-bioprocess network consisting of 178 C. elegans GIs. The GI network spans six annotated biological processes including aging, intracellular transport, microtubule-based processes, cytokinesis, lipid metabolic processes, and anatomical structure development. By proposing a strategy called "reciprocal functional test'' for interacting gene pairs, we discover a group of genes that mediate crosstalk between distinct biological processes. In particular, we identify the ribosomal S6 Kinase/RSKS-1, previously characterized as an mTOR (mechanistic target of rapamycin) effector, as a regulator of DAF-2 endosomal recycling transport, which traces a functional correlation between endocytic recycling and aging processes. Together, our results provide an alternative and effective strategy for identifying genes and pathways that mediate crosstalk between bioprocesses with little prior knowledge.