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RNR-R2 Upregulation by a Short Non-Coding Viral Transcript

Authors :
Karin Broennimann
Inna Ricardo-Lax
Julia Adler
Eleftherios Michailidis
Ype P. de Jong
Nina Reuven
Yosef Shaul
Source :
Biomolecules, Vol 11, Iss 12, p 1822 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

DNA viruses require dNTPs for replication and have developed different strategies to increase intracellular dNTP pools. Hepatitis B virus (HBV) infects non-dividing cells in which dNTPs are scarce and the question is how viral replication takes place. Previously we reported that the virus induces the DNA damage response (DDR) pathway culminating in RNR-R2 expression and the generation of an active RNR holoenzyme, the key regulator of dNTP levels, leading to an increase in dNTPs. How the virus induces DDR and RNR-R2 upregulation is not completely known. The viral HBx open reading frame (ORF) was believed to trigger this pathway. Unexpectedly, however, we report here that the production of HBx protein is dispensable. We found that a small conserved region of 125 bases within the HBx ORF is sufficient to upregulate RNR-R2 expression in growth-arrested HepG2 cells and primary human hepatocytes. The observed HBV mRNA embedded regulatory element is named ERE. ERE in isolation is sufficient to activate the ATR-Chk1-E2F1-RNR-R2 DDR pathway. These findings demonstrate a non-coding function of HBV transcripts to support its propagation in non-cycling cells.

Details

Language :
English
ISSN :
2218273X
Volume :
11
Issue :
12
Database :
Directory of Open Access Journals
Journal :
Biomolecules
Publication Type :
Academic Journal
Accession number :
edsdoj.0c6341ba99b446c49279ff1fe5ef0c21
Document Type :
article
Full Text :
https://doi.org/10.3390/biom11121822