Hepatitis B virus X protein recruits methyltransferases to affect cotranscriptional N6-methyladenosine modification of viral/host RNAs

Chronic hepatitis B virus (HBV) infections are one of the leading causes of cirrhosis and hepatocellular carcinoma. N6-methyladenosine (m A) modification of cellular and viral RNAs is the most prevalent internal modification that occurs cotranscriptionally. Previously, we reported the dual functiona...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 118; no. 3
Main Authors: Kim, Geon-Woo, Siddiqui, Aleem
Format: Journal Article
Language:English
Published: United States 19.01.2021
Subjects:
Adenosine - analogs & derivatives
Adenosine - genetics
Hep G2 Cells
Hepatitis B virus - genetics
Hepatitis B virus - pathogenicity
Hepatitis B, Chronic - genetics
Hepatitis B, Chronic - virology
Host-Pathogen Interactions - genetics
Humans
Methyltransferases - genetics
PTEN Phosphohydrolase - genetics
RNA Processing, Post-Transcriptional - genetics
RNA, Viral - genetics
Trans-Activators - genetics
Viral Regulatory and Accessory Proteins - genetics
Virus Replication - genetics
cotranscriptional modification
hepatitis B virus X protein
METTL3/14
N6-methyladenosine modification
hepatitis B virus
ISSN:1091-6490, 1091-6490
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Chronic hepatitis B virus (HBV) infections are one of the leading causes of cirrhosis and hepatocellular carcinoma. N6-methyladenosine (m A) modification of cellular and viral RNAs is the most prevalent internal modification that occurs cotranscriptionally. Previously, we reported the dual functional role of m A modification of HBV transcripts in the viral life cycle. Here, we show that viral HBV X (HBx) protein is responsible for the m A modifications of viral transcripts. HBV genomes defective in HBx failed to induce m A modifications of HBV RNAs during infection/transfection, while ectopic expression of HBx restores m A modifications of the viral RNAs but not the mutant HBx carrying the nuclear export signal. Using chromatin immunoprecipitation assays, we provide evidence that HBx and m A methyltransferase complexes are localized on the HBV minichromosome to achieve cotranscriptional m A modification of viral RNAs. HBx interacts with METTL3 and 14 to carry out methylation activity and also modestly stimulates their nuclear import. This role of HBx in mediating m A modification also extends to host phosphatase and tensin homolog (PTEN) mRNA. This study provides insight into how a viral protein recruits RNA methylation machinery to m A-modify RNAs.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.2019455118