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Multiple nuclear-replicating viruses require the stress-induced protein ZC3H11A for efficient growth.

Identifieur interne : 000978 ( Main/Exploration ); précédent : 000977; suivant : 000979

Multiple nuclear-replicating viruses require the stress-induced protein ZC3H11A for efficient growth.

Auteurs : Shady Younis [Suède] ; Wael Kamel [Suède] ; Tina Falkeborn [Suède] ; Hao Wang [Suède] ; Di Yu [Suède] ; Robert Daniels [Suède] ; Magnus Essand [Suède] ; Jorma Hinkula [Suède] ; Göran Akusj Rvi [Suède] ; Leif Andersson [Suède]

Source :

RBID : pubmed:29610341

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English descriptors

Abstract

The zinc finger CCCH-type containing 11A (ZC3H11A) gene encodes a well-conserved zinc finger protein that may function in mRNA export as it has been shown to associate with the transcription export (TREX) complex in proteomic screens. Here, we report that ZC3H11A is a stress-induced nuclear protein with RNA-binding capacity that localizes to nuclear splicing speckles. During an adenovirus infection, the ZC3H11A protein and splicing factor SRSF2 relocalize to nuclear regions where viral DNA replication and transcription take place. Knockout (KO) of ZC3H11A in HeLa cells demonstrated that several nuclear-replicating viruses are dependent on ZC3H11A for efficient growth (HIV, influenza virus, herpes simplex virus, and adenovirus), whereas cytoplasmic replicating viruses are not (vaccinia virus and Semliki Forest virus). High-throughput sequencing of ZC3H11A-cross-linked RNA showed that ZC3H11A binds to short purine-rich ribonucleotide stretches in cellular and adenoviral transcripts. We show that the RNA-binding property of ZC3H11A is crucial for its function and localization. In ZC3H11A KO cells, the adenovirus fiber mRNA accumulates in the cell nucleus. Our results suggest that ZC3H11A is important for maintaining nuclear export of mRNAs during stress and that several nuclear-replicating viruses take advantage of this mechanism to facilitate their replication.

DOI: 10.1073/pnas.1722333115
PubMed: 29610341


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<term>Adenoviruses, Human (genetics)</term>
<term>Adenoviruses, Human (physiology)</term>
<term>Binding Sites</term>
<term>Biological Transport</term>
<term>CRISPR-Cas Systems</term>
<term>Cell Nucleus (metabolism)</term>
<term>Cell Nucleus (virology)</term>
<term>Cytoplasm (virology)</term>
<term>Gene Knockout Techniques</term>
<term>HeLa Cells</term>
<term>Heat-Shock Response (genetics)</term>
<term>Heat-Shock Response (physiology)</term>
<term>High-Throughput Nucleotide Sequencing</term>
<term>Host-Pathogen Interactions</term>
<term>Humans</term>
<term>Nuclear Proteins (antagonists & inhibitors)</term>
<term>Nuclear Proteins (physiology)</term>
<term>Protein Domains</term>
<term>Protein Stability</term>
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<term>RNA, Viral (metabolism)</term>
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<term>RNA-Binding Proteins (physiology)</term>
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<term>ARN messager (métabolisme)</term>
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<term>Adénovirus humains (physiologie)</term>
<term>Cellules HeLa</term>
<term>Cytoplasme (virologie)</term>
<term>Doigts de zinc (physiologie)</term>
<term>Domaines protéiques</term>
<term>Facteurs d'épissage riches en sérine-arginine (physiologie)</term>
<term>Humains</term>
<term>Interactions hôte-pathogène</term>
<term>Noyau de la cellule (métabolisme)</term>
<term>Noyau de la cellule (virologie)</term>
<term>Protéines de liaison à l'ARN (antagonistes et inhibiteurs)</term>
<term>Protéines de liaison à l'ARN (physiologie)</term>
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<term>Protéines nucléaires (physiologie)</term>
<term>Réaction de choc thermique (génétique)</term>
<term>Réaction de choc thermique (physiologie)</term>
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<term>Sites de fixation</term>
<term>Stabilité protéique</term>
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<term>Techniques de knock-out de gènes</term>
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<term>Protéines nucléaires</term>
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<term>Heat-Shock Response</term>
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<term>Réaction de choc thermique</term>
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<term>RNA, Messenger</term>
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<term>Noyau de la cellule</term>
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<term>Adénovirus humains</term>
<term>Doigts de zinc</term>
<term>Facteurs d'épissage riches en sérine-arginine</term>
<term>Protéines de liaison à l'ARN</term>
<term>Protéines nucléaires</term>
<term>Réaction de choc thermique</term>
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<term>Adenoviruses, Human</term>
<term>Heat-Shock Response</term>
<term>Nuclear Proteins</term>
<term>RNA-Binding Proteins</term>
<term>Serine-Arginine Splicing Factors</term>
<term>Zinc Fingers</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr">
<term>Cytoplasme</term>
<term>Noyau de la cellule</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en">
<term>Cell Nucleus</term>
<term>Cytoplasm</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Binding Sites</term>
<term>Biological Transport</term>
<term>CRISPR-Cas Systems</term>
<term>Gene Knockout Techniques</term>
<term>HeLa Cells</term>
<term>High-Throughput Nucleotide Sequencing</term>
<term>Host-Pathogen Interactions</term>
<term>Humans</term>
<term>Protein Domains</term>
<term>Protein Stability</term>
<term>Virus Replication</term>
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<keywords scheme="MESH" xml:lang="fr">
<term>Cellules HeLa</term>
<term>Domaines protéiques</term>
<term>Humains</term>
<term>Interactions hôte-pathogène</term>
<term>Réplication virale</term>
<term>Sites de fixation</term>
<term>Stabilité protéique</term>
<term>Systèmes CRISPR-Cas</term>
<term>Séquençage nucléotidique à haut débit</term>
<term>Techniques de knock-out de gènes</term>
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<front>
<div type="abstract" xml:lang="en">The zinc finger CCCH-type containing 11A (
<i>ZC3H11A</i>
) gene encodes a well-conserved zinc finger protein that may function in mRNA export as it has been shown to associate with the transcription export (TREX) complex in proteomic screens. Here, we report that ZC3H11A is a stress-induced nuclear protein with RNA-binding capacity that localizes to nuclear splicing speckles. During an adenovirus infection, the ZC3H11A protein and splicing factor SRSF2 relocalize to nuclear regions where viral DNA replication and transcription take place. Knockout (KO) of
<i>ZC3H11A</i>
in HeLa cells demonstrated that several nuclear-replicating viruses are dependent on ZC3H11A for efficient growth (HIV, influenza virus, herpes simplex virus, and adenovirus), whereas cytoplasmic replicating viruses are not (vaccinia virus and Semliki Forest virus). High-throughput sequencing of ZC3H11A-cross-linked RNA showed that ZC3H11A binds to short purine-rich ribonucleotide stretches in cellular and adenoviral transcripts. We show that the RNA-binding property of ZC3H11A is crucial for its function and localization. In ZC3H11A KO cells, the adenovirus fiber mRNA accumulates in the cell nucleus. Our results suggest that ZC3H11A is important for maintaining nuclear export of mRNAs during stress and that several nuclear-replicating viruses take advantage of this mechanism to facilitate their replication.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Suède</li>
</country>
<region>
<li>Comté de Stockholm</li>
<li>East Middle Sweden</li>
<li>Svealand</li>
</region>
<settlement>
<li>Stockholm</li>
<li>Uppsala</li>
</settlement>
<orgName>
<li>Université d'Uppsala</li>
<li>Université de Stockholm</li>
</orgName>
</list>
<tree>
<country name="Suède">
<region name="Svealand">
<name sortKey="Younis, Shady" sort="Younis, Shady" uniqKey="Younis S" first="Shady" last="Younis">Shady Younis</name>
</region>
<name sortKey="Akusj Rvi, Goran" sort="Akusj Rvi, Goran" uniqKey="Akusj Rvi G" first="Göran" last="Akusj Rvi">Göran Akusj Rvi</name>
<name sortKey="Andersson, Leif" sort="Andersson, Leif" uniqKey="Andersson L" first="Leif" last="Andersson">Leif Andersson</name>
<name sortKey="Daniels, Robert" sort="Daniels, Robert" uniqKey="Daniels R" first="Robert" last="Daniels">Robert Daniels</name>
<name sortKey="Essand, Magnus" sort="Essand, Magnus" uniqKey="Essand M" first="Magnus" last="Essand">Magnus Essand</name>
<name sortKey="Falkeborn, Tina" sort="Falkeborn, Tina" uniqKey="Falkeborn T" first="Tina" last="Falkeborn">Tina Falkeborn</name>
<name sortKey="Hinkula, Jorma" sort="Hinkula, Jorma" uniqKey="Hinkula J" first="Jorma" last="Hinkula">Jorma Hinkula</name>
<name sortKey="Kamel, Wael" sort="Kamel, Wael" uniqKey="Kamel W" first="Wael" last="Kamel">Wael Kamel</name>
<name sortKey="Wang, Hao" sort="Wang, Hao" uniqKey="Wang H" first="Hao" last="Wang">Hao Wang</name>
<name sortKey="Yu, Di" sort="Yu, Di" uniqKey="Yu D" first="Di" last="Yu">Di Yu</name>
</country>
</tree>
</affiliations>
</record>

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