XRN1 incompletely hydrolyzes DENV decapped mRNA

Stable Identifier
R-HSA-9946917
Type
Reaction [uncertain]
Species
Homo sapiens
Related Species
Dengue virus type 2
Compartment
cytosol
ReviewStatus
5/5
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XRN1 incompletely hydrolyzes DENV decapped mRNA
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Host 5'-3' exoribonuclease 1 (XRN1) catalyzes the hydrolysis of DENV decapped mRNA from 5' to 3', yielding ribonucleotide-5'-monophosphates. The degradation stops at discrete elements of the DENV RNA 3′UTR that confer resistance to XRN1 (so called Xrn1-resistant RNA aka xrRNA) (Chapman et al., 2014a,b; MacFadden et al., 2018). The residual product of this incomplete degradation is referred to as small or subgenomic flaviviral RNA (sfRNA). Dengue viruses generate three to four distinct species of sfRNAs. They inhibit host antiviral responses by interacting with viral and host proteins (reviewed by Slonchak & Khromykh, 2018; Liu et al., 2023). sfRNAs appear to function as reversible inhibitors of XRN1 (Moon et al., 2012; Chapman et al., 2014a).
Literature References
PubMed ID Title Journal Year
30217649 Subgenomic flaviviral RNAs: What do we know after the first decade of research

Slonchak, A, Khromykh, AA

Antiviral Res 2018
38140548 Subgenomic Flaviviral RNAs of Dengue Viruses

Liu, Y, Guan, W, Liu, H

Viruses 2023
23006624 A noncoding RNA produced by arthropod-borne flaviviruses inhibits the cellular exoribonuclease XRN1 and alters host mRNA stability

Moon, SL, Anderson, JR, Kumagai, Y, Wilusz, CJ, Akira, S, Khromykh, AA, Wilusz, J

RNA 2012
24744377 The structural basis of pathogenic subgenomic flavivirus RNA (sfRNA) production

Chapman, EG, Costantino, DA, Rabe, JL, Moon, SL, Wilusz, J, Nix, JC, Kieft, JS

Science 2014
29317714 Mechanism and structural diversity of exoribonuclease-resistant RNA structures in flaviviral RNAs

MacFadden, A, O'Donoghue, Z, Silva, PAGC, Chapman, EG, Olsthoorn, RC, Sterken, MG, Pijlman, GP, Bredenbeek, PJ, Kieft, JS

Nat Commun 2018
24692447 RNA structures that resist degradation by Xrn1 produce a pathogenic Dengue virus RNA

Chapman, EG, Moon, SL, Wilusz, J, Kieft, JS

Elife 2014
Participants
Input
Output
Participates
as an event of
Event Information
Go Biological Process
mRNA catabolic process (0006402)
Catalyst Activity

5'-3' RNA exonuclease activity of XRN1 [cytosol]

Physical Entity
XRN1 [cytosol] (Homo sapiens)
Activity
5'-3' RNA exonuclease activity (GO:0004534)
This event is regulated
Negatively by
Regulator
DENV sfRNA [cytosol] (Dengue virus type 2)
Active Unit
XRN1 [cytosol]
Disease
Name Identifier Synonyms
dengue disease DOID:12205 breakbone fever, Dengue Fever, classic dengue
Cross References
Mondo
Authored
Stephan, R  (2025-04-28)
Reviewed
Mansur, DS  (2025-09-18)
Roque Ascenção, F  (2025-10-29)
Created
Stephan, R  (2025-04-29)
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