Biphasic regulation of RNA interference during rotavirus infection by modulation of Argonaute2

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Abstract

RNA interference (RNAi) is an evolutionary ancient innate immune response in plants, nematodes, and arthropods providing natural protection against viral infection. Viruses have also gained counter‐defensive measures by producing virulence determinants called viral‐suppressors‐of‐RNAi (VSRs). Interestingly, in spite of dominance of interferon‐based immunity over RNAi in somatic cells of higher vertebrates, recent reports are accumulating in favour of retention of the antiviral nature of RNAi in mammalian cells. The present study focuses on the modulation of intracellular RNAi during infection with rotavirus (RV), an enteric virus with double‐stranded RNA genome. Intriguingly, a time point‐dependent bimodal regulation of RNAi was observed in RV‐infected cells, where short interfering RNA (siRNA)‐based RNAi was rendered non‐functional during early hours of infection only to be reinstated fully beyond that early infection stage. Subsequent investigations revealed RV nonstructural protein 1 to serve as a putative VSR by associating with and triggering degradation of Argonaute2 (AGO2), the prime effector of siRNA‐mediated RNAi, via ubiquitin–proteasome pathway. The proviral significance of AGO2 degradation was further confirmed when ectopic overexpression of AGO2 significantly reduced RV infection. Cumulatively, the current study presents a unique modulation of host RNAi during RV infection, highlighting the importance of antiviral RNAi in mammalian cells.

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Most cited references 84

Record: found
Abstract: found
Article: not found

Argonaute2 is the catalytic engine of mammalian RNAi.

Jidong Liu, Michelle A Carmell, Fabiola V Rivas … (2004)

Gene silencing through RNA interference (RNAi) is carried out by RISC, the RNA-induced silencing complex. RISC contains two signature components, small interfering RNAs (siRNAs) and Argonaute family proteins. Here, we show that the multiple Argonaute proteins present in mammals are both biologically and biochemically distinct, with a single mammalian family member, Argonaute2, being responsible for messenger RNA cleavage activity. This protein is essential for mouse development, and cells lacking Argonaute2 are unable to mount an experimental response to siRNAs. Mutations within a cryptic ribonuclease H domain within Argonaute2, as identified by comparison with the structure of an archeal Argonaute protein, inactivate RISC. Thus, our evidence supports a model in which Argonaute contributes "Slicer" activity to RISC, providing the catalytic engine for RNAi.

0 comments Cited 757 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

Antiviral actions of interferons.

C Samuel (2001)

Tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), as well as strategies evolved by viruses to antagonize the actions of IFNs. Furthermore, advances made while elucidating the IFN system have contributed significantly to our understanding in multiple areas of virology and molecular cell biology, ranging from pathways of signal transduction to the biochemical mechanisms of transcriptional and translational control to the molecular basis of viral pathogenesis. IFNs are approved therapeutics and have moved from the basic research laboratory to the clinic. Among the IFN-induced proteins important in the antiviral actions of IFNs are the RNA-dependent protein kinase (PKR), the 2',5'-oligoadenylate synthetase (OAS) and RNase L, and the Mx protein GTPases. Double-stranded RNA plays a central role in modulating protein phosphorylation and RNA degradation catalyzed by the IFN-inducible PKR kinase and the 2'-5'-oligoadenylate-dependent RNase L, respectively, and also in RNA editing by the IFN-inducible RNA-specific adenosine deaminase (ADAR1). IFN also induces a form of inducible nitric oxide synthase (iNOS2) and the major histocompatibility complex class I and II proteins, all of which play important roles in immune response to infections. Several additional genes whose expression profiles are altered in response to IFN treatment and virus infection have been identified by microarray analyses. The availability of cDNA and genomic clones for many of the components of the IFN system, including IFN-alpha, IFN-beta, and IFN-gamma, their receptors, Jak and Stat and IRF signal transduction components, and proteins such as PKR, 2',5'-OAS, Mx, and ADAR, whose expression is regulated by IFNs, has permitted the generation of mutant proteins, cells that overexpress different forms of the proteins, and animals in which their expression has been disrupted by targeted gene disruption. The use of these IFN system reagents, both in cell culture and in whole animals, continues to provide important contributions to our understanding of the virus-host interaction and cellular antiviral response.

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Record: found
Abstract: found
Article: not found

RNA silencing in plants.

David Baulcombe (2004)

There are at least three RNA silencing pathways for silencing specific genes in plants. In these pathways, silencing signals can be amplified and transmitted between cells, and may even be self-regulated by feedback mechanisms. Diverse biological roles of these pathways have been established, including defence against viruses, regulation of gene expression and the condensation of chromatin into heterochromatin. We are now in a good position to investigate the full extent of this functional diversity in genetic and epigenetic mechanisms of genome control.

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Author and article information

Contributors

Mamta Chawla‐Sarkar:

ORCID: https://orcid.org/0000-0002-7141-1785

chawlam70@gmail.com , chawlasarkar.m@icmr.gov.in

Journal

Journal ID (nlm-ta): Cell Microbiol

Journal ID (iso-abbrev): Cell. Microbiol

Journal ID (doi): 10.1111/(ISSN)1462-5822

Journal ID (publisher-id): CMI

Title: Cellular Microbiology

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 1462-5814

ISSN (Electronic): 1462-5822

Publication date (Electronic): 26 August 2019

Publication date (Print): December 2019

Volume: 21

Issue: 12 ( doiID: 10.1111/cmi.v21.12 )

Electronic Location Identifier: e13101

Affiliations

[ ¹ ] Division of Virology National Institute of Cholera and Enteric Diseases Kolkata India

[ ² ] Department of Biotechnology GITAM Institute of Science Visakhapatnam India

[ ³ ] Department of Virology and Parasitology, School of Medicine Fujita Health University Aichi Japan

Author notes

[*] [* ] Correspondence

Mamta Chawla‐Sarkar, Division of Virology, National Institute of Cholera and Enteric Diseases, P‐33, C.I.T. Road, Scheme‐XM, Beliaghata, Kolkata 700010, West Bengal. India

Email: chawlam70@ 123456gmail.com ; chawlasarkar.m@ 123456icmr.gov.in

Author information

Mamta Chawla‐Sarkar https://orcid.org/0000-0002-7141-1785

Article

Publisher ID: CMI13101 Other ID: CMI-19-0058.R1

DOI: 10.1111/cmi.13101

PMC ID: 7162324

PubMed ID: 31424151

SO-VID: 82b6b78f-70e4-49ad-9c17-691f951d6120

License:

This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

History

Date received : 14 March 2019

Date revision received : 29 June 2019

Date accepted : 16 August 2019

Page count

Figures: 6, Tables: 2, Pages: 19, Words: 10614

Funding

Funded by: Okayama University Project through Japan Initiative for Global Research Network on Infectious Diseases (J‐GRID) of the Agency for Medical Research and Development (AMED)

Funded by: Science and Engineering Research Board; Dept. of Science and Technology (DST‐SERB)

Award ID: EMR/2016/001361

Custom metadata

source-schema-version-number 2.0

cover-date December 2019

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:16.04.2020

ScienceOpen disciplines: Microbiology & Virology

Keywords: argonaute2,nonstructural protein 1,rna interference,rotavirus,viral‐suppressors‐of‐rnai

Data availability:

ScienceOpen disciplines: Microbiology & Virology

Keywords: argonaute2, nonstructural protein 1, rna interference, rotavirus, viral‐suppressors‐of‐rnai

Biphasic regulation of RNA interference during rotavirus infection by modulation of Argonaute2

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