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

A549 Cells Fatty Acid Synthase, Type I / metabolism Gene Library Gene Ontology Humans Influenza A virus / drug effects Interferons / pharmacology Lipid Metabolism / drug effects Mutation / genetics Protein Binding / drug effects RNA, Messenger / genetics Viral Nonstructural Proteins / metabolism Virus Replication / drug effects

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
15 05 2020
Historique:
received: 19 03 2019
accepted: 13 04 2020
entrez: 17 5 2020
pubmed: 18 5 2020
medline: 13 8 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-020-16140-9 PMID: 32415096 PMC: PMC7229031
pubmed: 32415096
doi: 10.1038/s41467-020-16140-9
pii: 10.1038/s41467-020-16140-9
pmc: PMC7229031
doi:

Substances chimiques

INS1 protein, influenza virus 0
RNA, Messenger 0
Viral Nonstructural Proteins 0
Interferons 9008-11-1
FASN protein, human EC 2.3.1.85
Fatty Acid Synthase, Type I EC 2.3.1.85

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2449

Subventions

Organisme : NCI NIH HHS
ID : P01 CA177322
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI135972
Pays : United States

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Auteurs

Yushen Du (Y)

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA. lilyduyushen@g.ucla.edu.
Cancer Institute, ZJU-UCLA Joint Center for Medical Education and Research, School of Medicine, Zhejiang University, Hangzhou, 310058, China. lilyduyushen@g.ucla.edu.
ORCID: 0000-0002-8015-4207

Judd F Hultquist (JF)

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, 94158, USA.
California Institute for Quantitative Biosciences, QB3, University of California, San Francisco, San Francisco, CA, 94158, USA.
J. David Gladstone Institutes, San Francisco, CA, 94158, USA.
Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.

Quan Zhou (Q)

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.

Anders Olson (A)

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.

Yenwen Tseng (Y)

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.

Tian-Hao Zhang (TH)

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA.

Mengying Hong (M)

Cancer Institute, ZJU-UCLA Joint Center for Medical Education and Research, School of Medicine, Zhejiang University, Hangzhou, 310058, China.

Kejun Tang (K)

Cancer Institute, ZJU-UCLA Joint Center for Medical Education and Research, School of Medicine, Zhejiang University, Hangzhou, 310058, China.

Liubo Chen (L)

Cancer Institute, ZJU-UCLA Joint Center for Medical Education and Research, School of Medicine, Zhejiang University, Hangzhou, 310058, China.

Xiangzhi Meng (X)

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.

Michael J McGregor (MJ)

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, 94158, USA.
California Institute for Quantitative Biosciences, QB3, University of California, San Francisco, San Francisco, CA, 94158, USA.
J. David Gladstone Institutes, San Francisco, CA, 94158, USA.

Lei Dai (L)

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.

Danyang Gong (D)

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.

Laura Martin-Sancho (L)

Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.

Sumit Chanda (S)

Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.

Xinming Li (X)

Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, L, Los Angeles, CA, 90095, USA.

Steve Bensenger (S)

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA.
ORCID: 0000-0002-9657-4206

Nevan J Krogan (NJ)

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, 94158, USA.
California Institute for Quantitative Biosciences, QB3, University of California, San Francisco, San Francisco, CA, 94158, USA.
J. David Gladstone Institutes, San Francisco, CA, 94158, USA.
ORCID: 0000-0003-4902-337X

Ren Sun (R)

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA. rsun@mednet.ucla.edu.
Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA. rsun@mednet.ucla.edu.
ORCID: 0000-0002-8628-7019

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Classifications MeSH

questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules A549 › mRNA display with library of even-distribution...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Acyltransferases › Acyl-carrier protein S-malonyltransferase › Fatty acid synthases › Fatty acid synthase type I › mRNA display with library of even-distribution...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Banque de gènes › mRNA display with library of even-distribution...
questionsmedicales.fr › Sciences de l'information › Sources d'information › Services d'information › Documentation › Vocabulaire contrôlé › Ontologies biologiques › Gene Ontology › mRNA display with library of even-distribution...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › mRNA display with library of even-distribution...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN de polarité négative › Orthomyxoviridae › Influenzavirus A › Virus de la grippe A › mRNA display with library of even-distribution...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interférons › mRNA display with library of even-distribution...
questionsmedicales.fr › Métabolisme › Métabolisme lipidique › mRNA display with library of even-distribution...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › mRNA display with library of even-distribution...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › mRNA display with library of even-distribution...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › mRNA display with library of even-distribution...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales non structurales › mRNA display with library of even-distribution...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Réplication virale › mRNA display with library of even-distribution...