Abstract
We demonstrate that both Hepatitis C virus (HCV) and Bovine Viral Diarrhea virus (BVDV) contain regions in their 5’ UTRs that stall and repress the enzymatic activity of the cellular 5’-3’ exoribonuclease XRN1, resulting in dramatic changes in the stability of cellular mRNAs. We used biochemical assays, virus infections, and transfection of the HCV and BVDV 5’ untranslated regions in the absence of other viral gene products to directly demonstrate the existence and mechanism of this novel host-virus interaction. In the context of HCV infection, we observed globally increased stability of mRNAs resulting in significant increases in abundance of normally short-lived mRNAs encoding a variety of relevant oncogenes and angiogenesis factors. These findings suggest that non-coding regions from multiple genera of the Flaviviridae interfere with XRN1 and impact post-transcriptional processes, causing global dysregulation of cellular gene expression which may promote cell growth and pathogenesis.
| Original language | English (US) |
|---|---|
| Article number | e1004708 |
| Pages (from-to) | 1-21 |
| Number of pages | 21 |
| Journal | PLoS Pathogens |
| Volume | 11 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2015 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Microbiology
- Parasitology
- Virology
- Immunology
- Genetics
- Molecular Biology
Cite this
XRN1 Stalling in the 5’ UTR of Hepatitis C Virus and Bovine Viral Diarrhea Virus Is Associated with Dysregulated Host mRNA Stability. / Moon, Stephanie L.; Blackinton, Jeffrey G.; Anderson, John R.; Dozier, Mary K.; Dodd, Benjamin J T; Keene, Jack D.; Wilusz, Carol J.; Bradrick, Shelton; Wilusz, Jeffrey.
In: PLoS Pathogens, Vol. 11, No. 3, e1004708, 01.03.2015, p. 1-21.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - XRN1 Stalling in the 5’ UTR of Hepatitis C Virus and Bovine Viral Diarrhea Virus Is Associated with Dysregulated Host mRNA Stability
AU - Moon, Stephanie L.
AU - Blackinton, Jeffrey G.
AU - Anderson, John R.
AU - Dozier, Mary K.
AU - Dodd, Benjamin J T
AU - Keene, Jack D.
AU - Wilusz, Carol J.
AU - Bradrick, Shelton
AU - Wilusz, Jeffrey
PY - 2015/3/1
Y1 - 2015/3/1
N2 - We demonstrate that both Hepatitis C virus (HCV) and Bovine Viral Diarrhea virus (BVDV) contain regions in their 5’ UTRs that stall and repress the enzymatic activity of the cellular 5’-3’ exoribonuclease XRN1, resulting in dramatic changes in the stability of cellular mRNAs. We used biochemical assays, virus infections, and transfection of the HCV and BVDV 5’ untranslated regions in the absence of other viral gene products to directly demonstrate the existence and mechanism of this novel host-virus interaction. In the context of HCV infection, we observed globally increased stability of mRNAs resulting in significant increases in abundance of normally short-lived mRNAs encoding a variety of relevant oncogenes and angiogenesis factors. These findings suggest that non-coding regions from multiple genera of the Flaviviridae interfere with XRN1 and impact post-transcriptional processes, causing global dysregulation of cellular gene expression which may promote cell growth and pathogenesis.
AB - We demonstrate that both Hepatitis C virus (HCV) and Bovine Viral Diarrhea virus (BVDV) contain regions in their 5’ UTRs that stall and repress the enzymatic activity of the cellular 5’-3’ exoribonuclease XRN1, resulting in dramatic changes in the stability of cellular mRNAs. We used biochemical assays, virus infections, and transfection of the HCV and BVDV 5’ untranslated regions in the absence of other viral gene products to directly demonstrate the existence and mechanism of this novel host-virus interaction. In the context of HCV infection, we observed globally increased stability of mRNAs resulting in significant increases in abundance of normally short-lived mRNAs encoding a variety of relevant oncogenes and angiogenesis factors. These findings suggest that non-coding regions from multiple genera of the Flaviviridae interfere with XRN1 and impact post-transcriptional processes, causing global dysregulation of cellular gene expression which may promote cell growth and pathogenesis.
UR - http://www.scopus.com/inward/record.url?scp=84926451436&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84926451436&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.1004708
DO - 10.1371/journal.ppat.1004708
M3 - Article
C2 - 25747802
AN - SCOPUS:84926451436
VL - 11
SP - 1
EP - 21
JO - PLoS Pathogens
JF - PLoS Pathogens
SN - 1553-7366
IS - 3
M1 - e1004708
ER -