Artikel ; Online: Zika virus noncoding sfRNAs sequester multiple host-derived RNA-binding proteins and modulate mRNA decay and splicing during infection.
The Journal of biological chemistry
2019 Band 294, Heft 44, Seite(n) 16282–16296
Abstract: Insect-borne flaviviruses produce a 300-500-base long noncoding RNA, termed subgenomic flavivirus RNA (sfRNA), by stalling the cellular 5'-3'-exoribonuclease 1 (XRN1) via structures located in their 3' UTRs. In this study, we demonstrate that sfRNA ... ...
| Abstract | Insect-borne flaviviruses produce a 300-500-base long noncoding RNA, termed subgenomic flavivirus RNA (sfRNA), by stalling the cellular 5'-3'-exoribonuclease 1 (XRN1) via structures located in their 3' UTRs. In this study, we demonstrate that sfRNA production by Zika virus represses XRN1 analogous to what we have previously shown for other flaviviruses. Using protein-RNA reconstitution and a stringent RNA pulldown assay with human choriocarcinoma (JAR) cells, we demonstrate that the sfRNAs from both dengue type 2 and Zika viruses interact with a common set of 21 RNA-binding proteins that contribute to the regulation of post-transcriptional processes in the cell, including splicing, RNA stability, and translation. We found that four of these sfRNA-interacting host proteins, DEAD-box helicase 6 (DDX6) and enhancer of mRNA decapping 3 (EDC3) (two RNA decay factors), phosphorylated adaptor for RNA export (a regulator of the biogenesis of the splicing machinery), and apolipoprotein B mRNA-editing enzyme catalytic subunit 3C (APOBEC3C, a nucleic acid-editing deaminase), inherently restrict Zika virus infection. Furthermore, we demonstrate that the regulations of cellular mRNA decay and RNA splicing are compromised by Zika virus infection as well as by sfRNA alone. Collectively, these results reveal the large extent to which Zika virus-derived sfRNAs interact with cellular RNA-binding proteins and highlight the potential for widespread dysregulation of post-transcriptional control that likely limits the effective response of these cells to viral infection. |
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| Mesh-Begriff(e) | 3' Untranslated Regions ; Animals ; Chlorocebus aethiops ; DEAD-box RNA Helicases/metabolism ; Exoribonucleases/metabolism ; Flavivirus/genetics ; Genome, Viral/genetics ; HEK293 Cells ; Host-Pathogen Interactions ; Humans ; Microtubule-Associated Proteins/metabolism ; Nucleic Acid Conformation ; Proto-Oncogene Proteins/metabolism ; RNA Splicing/physiology ; RNA Stability/physiology ; RNA, Messenger/metabolism ; RNA, Untranslated/genetics ; RNA, Untranslated/metabolism ; RNA, Viral/metabolism ; RNA-Binding Proteins/metabolism ; Ribonucleoproteins, Small Nuclear/metabolism ; Vero Cells ; Zika Virus/genetics ; Zika Virus/metabolism ; Zika Virus Infection/virology | |||||
| Chemische Substanzen | 3' Untranslated Regions ; EDC3 protein, human ; Microtubule-Associated Proteins ; Proto-Oncogene Proteins ; RNA, Messenger ; RNA, Untranslated ; RNA, Viral ; RNA-Binding Proteins ; Ribonucleoproteins, Small Nuclear ; Exoribonucleases (EC 3.1.-) ; XRN1 protein, human (EC 3.1.13.1) ; DDX6 protein, human (EC 3.6.1.-) ; DEAD-box RNA Helicases (EC 3.6.4.13) | |||||
| Sprache | Englisch | |||||
| Erscheinungsdatum | 2019-09-13 | |||||
| Erscheinungsland | United States | |||||
| Dokumenttyp | Journal Article ; Research Support, N.I.H., Extramural | |||||
| ZDB-ID | 2997-x | |||||
| ISSN | 1083-351X ; 0021-9258 | |||||
| ISSN (online) | 1083-351X | |||||
| ISSN | 0021-9258 | |||||
| DOI | 10.1074/jbc.RA119.009129 | |||||
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| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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