mRNA display with library of even-distribution reveals cellular interactors of influenza virus NS1

Yushen Du; Judd F. Hultquist; Quan Zhou; Anders Olson; Yenwen Tseng; Tian hao Zhang; Mengying Hong; Kejun Tang; Liubo Chen; Xiangzhi Meng; Michael J. McGregor; Lei Dai; Danyang Gong; Laura Martin-Sancho; Sumit Chanda; Xinming Li; Steve Bensenger; Nevan J. Krogan; Ren Sun

doi:10.1038/s41467-020-16140-9

mRNA display with library of even-distribution reveals cellular interactors of influenza virus NS1

Yushen Du^*, Judd F. Hultquist, Quan Zhou, Anders Olson, Yenwen Tseng, Tian hao Zhang, Mengying Hong, Kejun Tang, Liubo Chen, Xiangzhi Meng, Michael J. McGregor, Lei Dai, Danyang Gong, Laura Martin-Sancho, Sumit Chanda, Xinming Li, Steve Bensenger, Nevan J. Krogan, Ren Sun

^*Corresponding author for this work

Medicine, Infectious Diseases Division

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

Abstract

A comprehensive examination of protein-protein interactions (PPIs) is fundamental for the understanding of cellular machineries. However, limitations in current methodologies often prevent the detection of PPIs with low abundance proteins. To overcome this challenge, we develop a mRNA display with library of even-distribution (md-LED) method that facilitates the detection of low abundance binders with high specificity and sensitivity. As a proof-of-principle, we apply md-LED to IAV NS1 protein. Complementary to AP-MS, md-LED enables us to validate previously described PPIs as well as to identify novel NS1 interactors. We show that interacting with FASN allows NS1 to directly regulate the synthesis of cellular fatty acids. We also use md-LED to identify a mutant of NS1, D92Y, results in a loss of interaction with CPSF1. The use of high-throughput sequencing as the readout for md-LED enables sensitive quantification of interactions, ultimately enabling massively parallel experimentation for the investigation of PPIs.

Original language	English (US)
Article number	2449
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-16140-9
State	Published - Dec 1 2020

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Du, Y., Hultquist, J. F., Zhou, Q., Olson, A., Tseng, Y., Zhang, T. H., Hong, M., Tang, K., Chen, L., Meng, X., McGregor, M. J., Dai, L., Gong, D., Martin-Sancho, L., Chanda, S., Li, X., Bensenger, S., Krogan, N. J., & Sun, R. (2020). mRNA display with library of even-distribution reveals cellular interactors of influenza virus NS1. Nature communications, 11(1), [2449]. https://doi.org/10.1038/s41467-020-16140-9

Du, Yushen ; Hultquist, Judd F. ; Zhou, Quan ; Olson, Anders ; Tseng, Yenwen ; Zhang, Tian hao ; Hong, Mengying ; Tang, Kejun ; Chen, Liubo ; Meng, Xiangzhi ; McGregor, Michael J. ; Dai, Lei ; Gong, Danyang ; Martin-Sancho, Laura ; Chanda, Sumit ; Li, Xinming ; Bensenger, Steve ; Krogan, Nevan J. ; Sun, Ren. / mRNA display with library of even-distribution reveals cellular interactors of influenza virus NS1. In: Nature communications. 2020 ; Vol. 11, No. 1.

@article{e15c8331cbda4844a15f356b66bbdeaf,

title = "mRNA display with library of even-distribution reveals cellular interactors of influenza virus NS1",

abstract = "A comprehensive examination of protein-protein interactions (PPIs) is fundamental for the understanding of cellular machineries. However, limitations in current methodologies often prevent the detection of PPIs with low abundance proteins. To overcome this challenge, we develop a mRNA display with library of even-distribution (md-LED) method that facilitates the detection of low abundance binders with high specificity and sensitivity. As a proof-of-principle, we apply md-LED to IAV NS1 protein. Complementary to AP-MS, md-LED enables us to validate previously described PPIs as well as to identify novel NS1 interactors. We show that interacting with FASN allows NS1 to directly regulate the synthesis of cellular fatty acids. We also use md-LED to identify a mutant of NS1, D92Y, results in a loss of interaction with CPSF1. The use of high-throughput sequencing as the readout for md-LED enables sensitive quantification of interactions, ultimately enabling massively parallel experimentation for the investigation of PPIs.",

author = "Yushen Du and Hultquist, {Judd F.} and Quan Zhou and Anders Olson and Yenwen Tseng and Zhang, {Tian hao} and Mengying Hong and Kejun Tang and Liubo Chen and Xiangzhi Meng and McGregor, {Michael J.} and Lei Dai and Danyang Gong and Laura Martin-Sancho and Sumit Chanda and Xinming Li and Steve Bensenger and Krogan, {Nevan J.} and Ren Sun",

note = "Funding Information: Funding support of NIH PO1 CA177322 to R.S., S.C., and N.K. and NIH U19AI135972.",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-16140-9",

language = "English (US)",

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journal = "Nature Communications",

issn = "2041-1723",

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Du, Y, Hultquist, JF, Zhou, Q, Olson, A, Tseng, Y, Zhang, TH, Hong, M, Tang, K, Chen, L, Meng, X, McGregor, MJ, Dai, L, Gong, D, Martin-Sancho, L, Chanda, S, Li, X, Bensenger, S, Krogan, NJ & Sun, R 2020, 'mRNA display with library of even-distribution reveals cellular interactors of influenza virus NS1', Nature communications, vol. 11, no. 1, 2449. https://doi.org/10.1038/s41467-020-16140-9

mRNA display with library of even-distribution reveals cellular interactors of influenza virus NS1. / Du, Yushen; Hultquist, Judd F.; Zhou, Quan; Olson, Anders; Tseng, Yenwen; Zhang, Tian hao; Hong, Mengying; Tang, Kejun; Chen, Liubo; Meng, Xiangzhi; McGregor, Michael J.; Dai, Lei; Gong, Danyang; Martin-Sancho, Laura; Chanda, Sumit; Li, Xinming; Bensenger, Steve; Krogan, Nevan J.; Sun, Ren.

In: Nature communications, Vol. 11, No. 1, 2449, 01.12.2020.

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

TY - JOUR

T1 - mRNA display with library of even-distribution reveals cellular interactors of influenza virus NS1

AU - Du, Yushen

AU - Hultquist, Judd F.

AU - Zhou, Quan

AU - Olson, Anders

AU - Tseng, Yenwen

AU - Zhang, Tian hao

AU - Hong, Mengying

AU - Tang, Kejun

AU - Chen, Liubo

AU - Meng, Xiangzhi

AU - McGregor, Michael J.

AU - Dai, Lei

AU - Gong, Danyang

AU - Martin-Sancho, Laura

AU - Chanda, Sumit

AU - Li, Xinming

AU - Bensenger, Steve

AU - Krogan, Nevan J.

AU - Sun, Ren

N1 - Funding Information: Funding support of NIH PO1 CA177322 to R.S., S.C., and N.K. and NIH U19AI135972.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - A comprehensive examination of protein-protein interactions (PPIs) is fundamental for the understanding of cellular machineries. However, limitations in current methodologies often prevent the detection of PPIs with low abundance proteins. To overcome this challenge, we develop a mRNA display with library of even-distribution (md-LED) method that facilitates the detection of low abundance binders with high specificity and sensitivity. As a proof-of-principle, we apply md-LED to IAV NS1 protein. Complementary to AP-MS, md-LED enables us to validate previously described PPIs as well as to identify novel NS1 interactors. We show that interacting with FASN allows NS1 to directly regulate the synthesis of cellular fatty acids. We also use md-LED to identify a mutant of NS1, D92Y, results in a loss of interaction with CPSF1. The use of high-throughput sequencing as the readout for md-LED enables sensitive quantification of interactions, ultimately enabling massively parallel experimentation for the investigation of PPIs.

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