دورية أكاديمية

Zinc Finger Protein ZFP36L1 Inhibits Flavivirus Infection by both 5'-3' XRN1 and 3'-5' RNA-Exosome RNA Decay Pathways.

التفاصيل البيبلوغرافية
العنوان: Zinc Finger Protein ZFP36L1 Inhibits Flavivirus Infection by both 5'-3' XRN1 and 3'-5' RNA-Exosome RNA Decay Pathways.
المؤلفون: Chiu H; Graduate Institute of Microbiology, National Taiwan University, Taipei, Taiwan.; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Chiu HP; Graduate Institute of Microbiology, National Taiwan University, Taipei, Taiwan.; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Yu HP; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Lin LH; National Mosquito-Borne Diseases Control Research Center, National Health Research Institute, Taipei, Taiwan., Chen ZP; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan., Lin YL; Graduate Institute of Microbiology, National Taiwan University, Taipei, Taiwan.; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.; Genomics Research Center, Academia Sinica, Taipei, Taiwan., Lin RJ; National Mosquito-Borne Diseases Control Research Center, National Health Research Institute, Taipei, Taiwan.; Ph.D. Program in Medical Biotechnology, Taipei Medical University, Taipei, Taiwan.
المصدر: Journal of virology [J Virol] 2022 Jan 12; Vol. 96 (1), pp. e0166521. Date of Electronic Publication: 2021 Oct 13.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE
أسماء مطبوعة: Publication: Washington Dc : American Society For Microbiology
Original Publication: Baltimore, American Society for Microbiology.
مواضيع طبية MeSH: RNA Stability* , Virus Replication*, Butyrate Response Factor 1/*metabolism , Exoribonucleases/*metabolism , Exosome Multienzyme Ribonuclease Complex/*metabolism , Flavivirus/*physiology , Flavivirus Infections/*metabolism , Flavivirus Infections/*virology , Microtubule-Associated Proteins/*metabolism, 3' Untranslated Regions ; Amino Acid Motifs ; Butyrate Response Factor 1/chemistry ; Dengue Virus/physiology ; Encephalitis Virus, Japanese/physiology ; Host-Pathogen Interactions ; Humans ; Protein Binding ; Protein Interaction Domains and Motifs ; RNA, Viral/genetics ; RNA, Viral/metabolism ; RNA-Binding Proteins
مستخلص: Zinc-finger protein 36, CCCH type-like 1 (ZFP36L1), containing tandem CCCH-type zinc-finger motifs with an RNA-binding property, plays an important role in cellular RNA metabolism mainly by RNA decay pathways. Recently, we demonstrated that human ZFP36L1 has potent antiviral activity against influenza A virus infection. However, its role in the host defense response against flaviviruses has not been addressed. Here, we demonstrate that ZFP36L1 functions as a host innate defender against flaviviruses, including Japanese encephalitis virus (JEV) and dengue virus (DENV). Overexpression of ZFP36L1 reduced JEV and DENV infection, and ZFP36L1 knockdown enhanced viral replication. ZFP36L1 destabilized the JEV genome by targeting and degrading viral RNA mediated by both 5'-3' XRN1 and 3'-5' RNA-exosome RNA decay pathways. Mutation in both zinc-finger motifs of ZFP36L1 disrupted RNA-binding and antiviral activity. Furthermore, the viral RNA sequences specifically recognized by ZFP36L1 were mapped to the 3'-untranslated region of the JEV genome with the AU-rich element (AUUUA) motif. We extend the function of ZFP36L1 to host antiviral defense by directly binding and destabilizing the viral genome via recruiting cellular mRNA decay machineries. IMPORTANCE Cellular RNA-binding proteins are among the first lines of defense against various viruses, particularly RNA viruses. ZFP36L1 belongs to the CCCH-type zinc-finger protein family and has RNA-binding activity; it has been reported to bind directly to the AU-rich elements (AREs) of a subset of cellular mRNAs and then lead to mRNA decay by recruiting mRNA-degrading enzymes. However, the antiviral potential of ZFP36L1 against flaviviruses has not yet been fully demonstrated. Here, we reveal the antiviral potential of human ZFP36L1 against Japanese encephalitis virus (JEV) and dengue virus (DENV). ZFP36L1 specifically targeted the ARE motif within viral RNA and triggered the degradation of viral RNA transcripts via cellular degrading enzymes 5'-3' XRN1 and 3'-5' RNA exosome. These findings provide mechanistic insights into how human ZFP36L1 serves as a host antiviral factor to restrict flavivirus replication.
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فهرسة مساهمة: Keywords: ZFP36L1; antiviral mechanism; flavivirus; zinc-finger RNA-binding protein
المشرفين على المادة: 0 (3' Untranslated Regions)
0 (Butyrate Response Factor 1)
0 (Microtubule-Associated Proteins)
0 (RNA, Viral)
0 (RNA-Binding Proteins)
0 (ZFP36L1 protein, human)
EC 3.1.- (Exoribonucleases)
EC 3.1.- (Exosome Multienzyme Ribonuclease Complex)
EC 3.1.13.1 (XRN1 protein, human)
تواريخ الأحداث: Date Created: 20211013 Date Completed: 20220221 Latest Revision: 20220716
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8754223
DOI: 10.1128/JVI.01665-21
PMID: 34643435
قاعدة البيانات: MEDLINE
الوصف
تدمد:1098-5514
DOI:10.1128/JVI.01665-21