RBM24 Stabilizes Hepatitis B Virus Pregenomic RNA but Inhibits Core Protein Translation by Targeting the Terminal Redundancy Sequence

Overview

Journal Emerg Microbes Infect

Specialty Infectious Diseases

Date 2018 May 16

PMID 29760415

Citations 16

Authors

Yongxuan Yao

Bo Yang

Huang Cao

Kaitao Zhao

Yifei Yuan

Yingshan Chen

Zhenhua Zhang

Yun Wang

Rongjuan Pei

Jizheng Chen

Xue Hu

Yuan Zhou

Mengji Lu

Chunchen Wu

Xinwen Chen

Affiliations

Soon will be listed here.

Abstract

The terminal redundancy (TR) sequence of the 3.5-kb hepatitis B virus (HBV) RNA contains sites that govern many crucial functions in the viral life cycle, including polyadenylation, translation, RNA packaging, and DNA synthesis. In the present study, RNA-binding motif protein 24 (RBM24) is shown to be involved in the modulation of HBV replication by targeting the TR of HBV RNA. In HBV-transfected hepatoma cell lines, both knockdown and overexpression of RBM24 led to decreased HBV replication and transcription. Ectopic expression of RBM24 inhibited HBV replication, which was partly restored by knockdown of RBM24, indicating that a proper level of RBM24 was required for HBV replication. The regulation of RBM24 of HBV replication and translation was achieved by the interaction between the RNA-binding domains of RBM24 and both the 5' and 3' TR of 3.5-kb RNA. RBM24 interacted with the 5' TR of HBV pregenomic RNA (pgRNA) to block 80S ribosome assembly on HBV pgRNA and thus inhibited core protein translation, whereas the interaction between RBM24 and the 3' TR enhanced the stability of HBV RNA. Finally, the regulatory function of RBM24 on HBV replication was further confirmed in a HBV infection model. In conclusion, the present study demonstrates the dual functions of RBM24 by interacting with different TRs of viral RNA and reveals that RBM24 is an important host gene for HBV replication.

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