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.
|Original language||English (US)|
|State||Published - Nov 26 2019|
Bibliographical noteFunding Information:
We thank Charles Boone, Kang Shen, Guangshuo Ou, and Di Chen for their support and discussions regarding this work. We thank Peter Schweinsberg and Jia Zeng for the technical assistance. This work was supported by NIH grant R01GM067237 to B.D.G.; NIH grant R01HG005084 , the National Science Foundation ( DBI\0953881 ), and the Canadian Institute for Advanced Research (CIFAR) to C.L.M.; the National Science Fund for Distinguished Young Scholars ( 31825017 ), the Major Research Plan of the National Natural Science Foundation of China (Organellar interactome for cellular homeostasis), the National Natural Science Foundation of China ( 31571466 and 31771570 ), the Ministry of Science and Technology of China ( 2017YFE0120300 ), and the Natural Science Foundation of Hubei Province of China ( 2018CFA017 ) to A.S.; and the National Natural Science Foundation of China ( 61571202 ) and the Junior Thousand Talents Program of China to T.X.
© 2019 The Authors
- Caenorhabditis elegans
- RSKS-1/S6 Kinase
- Saccharomyces cerevisiae
- bioprocess crosstalk
- comparative mapping
- endocytic recycling
- genetic interaction
- recycling endosomes