Revealing Functional Crosstalk between Distinct Bioprocesses through Reciprocal Functional Tests of Genetically Interacting Genes

Dan Chen; Wei Xu; Yu Wang; Yongshen Ye; Yue Wang; Miao Yu; Jinghu Gao; Jielin Wei; Yiming Dong; Honghua Zhang; Xin Fu; Ke Ma; Hui Wang; Zhenrong Yang; Jie Zhou; Wenqing Cheng; Shu Wang; Juan Chen; Barth D. Grant; Chad L. Myers; Anbing Shi; Tian Xia

doi:10.1016/j.celrep.2019.10.076

Revealing Functional Crosstalk between Distinct Bioprocesses through Reciprocal Functional Tests of Genetically Interacting Genes

Dan Chen, Wei Xu, Yu Wang, Yongshen Ye, Yue Wang, Miao Yu, Jinghu Gao, Jielin Wei, Yiming Dong, Honghua Zhang, Xin Fu, Ke Ma, Hui Wang, Zhenrong Yang, Jie Zhou, Wenqing Cheng, Shu Wang, Juan Chen, Barth D. Grant, Chad L. MyersAnbing Shi, Tian Xia

Computer Science and Engineering

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

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)
Pages (from-to)	2646-2658.e5
Journal	Cell reports
Volume	29
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2019.10.076
State	Published - Nov 26 2019

Bibliographical note

Funding 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.

Publisher Copyright:
© 2019 The Authors

Keywords

Caenorhabditis elegans
RAB-10/Rab10
RSKS-1/S6 Kinase
Saccharomyces cerevisiae
bioprocess crosstalk
comparative mapping
endocytic recycling
genetic interaction
mTOR
recycling endosomes

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10.1016/j.celrep.2019.10.076

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Chen, D., Xu, W., Wang, Y., Ye, Y., Wang, Y., Yu, M., Gao, J., Wei, J., Dong, Y., Zhang, H., Fu, X., Ma, K., Wang, H., Yang, Z., Zhou, J., Cheng, W., Wang, S., Chen, J., Grant, B. D., ... Xia, T. (2019). Revealing Functional Crosstalk between Distinct Bioprocesses through Reciprocal Functional Tests of Genetically Interacting Genes. Cell reports, 29(9), 2646-2658.e5. https://doi.org/10.1016/j.celrep.2019.10.076

Chen, D, Xu, W, Wang, Y, Ye, Y, Wang, Y, Yu, M, Gao, J, Wei, J, Dong, Y, Zhang, H, Fu, X, Ma, K, Wang, H, Yang, Z, Zhou, J, Cheng, W, Wang, S, Chen, J, Grant, BD, Myers, CL, Shi, A & Xia, T 2019, 'Revealing Functional Crosstalk between Distinct Bioprocesses through Reciprocal Functional Tests of Genetically Interacting Genes', Cell reports, vol. 29, no. 9, pp. 2646-2658.e5. https://doi.org/10.1016/j.celrep.2019.10.076

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title = "Revealing Functional Crosstalk between Distinct Bioprocesses through Reciprocal Functional Tests of Genetically Interacting Genes",

abstract = "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.",

keywords = "Caenorhabditis elegans, RAB-10/Rab10, RSKS-1/S6 Kinase, Saccharomyces cerevisiae, bioprocess crosstalk, comparative mapping, endocytic recycling, genetic interaction, mTOR, recycling endosomes",

author = "Dan Chen and Wei Xu and Yu Wang and Yongshen Ye and Yue Wang and Miao Yu and Jinghu Gao and Jielin Wei and Yiming Dong and Honghua Zhang and Xin Fu and Ke Ma and Hui Wang and Zhenrong Yang and Jie Zhou and Wenqing Cheng and Shu Wang and Juan Chen and Grant, {Barth D.} and Myers, {Chad L.} and Anbing Shi and Tian Xia",

note = "Funding 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. Publisher Copyright: {\textcopyright} 2019 The Authors",

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doi = "10.1016/j.celrep.2019.10.076",

language = "English (US)",

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AU - Chen, Dan

AU - Xu, Wei

AU - Wang, Yu

AU - Ye, Yongshen

AU - Wang, Yue

AU - Yu, Miao

AU - Gao, Jinghu

AU - Wei, Jielin

AU - Dong, Yiming

AU - Zhang, Honghua

AU - Fu, Xin

AU - Ma, Ke

AU - Wang, Hui

AU - Yang, Zhenrong

AU - Zhou, Jie

AU - Cheng, Wenqing

AU - Wang, Shu

AU - Chen, Juan

AU - Grant, Barth D.

AU - Myers, Chad L.

AU - Shi, Anbing

AU - Xia, Tian

N1 - Funding 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. Publisher Copyright: © 2019 The Authors

PY - 2019/11/26

Y1 - 2019/11/26

N2 - 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.

AB - 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.

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KW - RSKS-1/S6 Kinase

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KW - comparative mapping

KW - endocytic recycling

KW - genetic interaction

KW - mTOR

KW - recycling endosomes

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Revealing Functional Crosstalk between Distinct Bioprocesses through Reciprocal Functional Tests of Genetically Interacting Genes

Abstract

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Keywords

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