RNA-Binding motif protein 38 (RBM38) mediates HBV pgRNA packaging into the nucleocapsid

Yao, Yongxuan; Yang, Bo; Chen, Yingshan; Huang, Dan; Liu, Canyu; Sun, Hao; Zhou, Yuan; Wang, Yun; Chen, Jizheng; Pei, Rongjuan; Wang, Zhe; Chen, Xinwen

doi:10.1016/j.antiviral.2022.105249

Cited by 8 publications

(12 citation statements)

References 39 publications

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“…resulted in an increase of HBV RNAs, both total RNAs and pgRNA, without significantly affecting cccDNA levels (Figure 5C and E). These results indicate that, as previously reported for some other cellular RBPs, these factors behave as anti-viral factor that exert their functions at transcriptional and/or post-transcriptional level (Sun et al, 2017;Yao et al, 2018;Yao et al, 2019;Chabrolles et al, 2020;Yao et al, 2023b ).…”

Section: Hnrnpu and Srrm2 Two Rbps Up-phosphorylated Upon Hbv Infecti...supporting

confidence: 87%

Deciphering the phospho-signature induced by hepatitis B virus in primary human hepatocytes

Pastor,

Charles,

Belmudes

et al. 2024

Preprint

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Phosphorylation is a major post-translation modification (PTM) of proteins, and small molecules, which is finely tuned by the activity of several hundred kinases and phosphatases. It controls most if not all cellular pathways including anti-viral responses. Accordingly, viruses often induce important changes in the phosphorylation of host factors that can either help or counteract viral replication. Among more than 500 kinases constituting the human kinome only few have been described as important for the Hepatitis B virus (HBV) infectious cycle, and most of them intervene during early or late infectious steps by phosphorylating the viral Core protein (HBc) protein. In addition, scarce information is available on the consequences of HBV infection on the activity of cellular kinases. The objective of this study was to investigate the global impact of HBV infection on the cellular phosphorylation landscape at early after infection. For this, primary human hepatocytes (PHH) were challenged or not with HBV, and a mass spectrometry (MS)-based quantitative phosphoproteomic analysis was conducted two- and seven-days post-infection. The results indicated that while, as expected, HBV infection only minimally modified the cell proteome, important changes were observed on the phosphorylation level of several host proteins at both times points. Gene enrichment and ontology analyses of up- and down- phosphorylated proteins revealed common and distinct signatures induced following infection. In particular, HBV infection resulted in up-phosphorylation of proteins involved in DNA damage signaling and repair, RNA metabolism, in particular splicing, and cytoplasmic cell-signaling. Several down-phosphorylated factors, mostly involved in cell signaling and communication, were also detected. Validation studies performed on some selected up-phosphorylated proteins, revealed that HBV infection induced a DNA damage response characterized by the appearance of 53BP1 foci, whose siRNA-mediated knock-down increased cccDNA levels. In addition, among up-phosphorylated RBPs, SRRM2, a major scaffold of nuclear speckles behaved as antiviral factor. In accordance with these findings, kinase prediction analysis indicated that HBV infection upregulates the activity of major kinases involved in DNA repair. These results strongly suggest that HBV infection triggers an intrinsic anti-viral response composed by DNA repair factors and RBPs that contribute to reduce HBV replication in cell culture models.

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Section: Hnrnpu and Srrm2 Two Rbps Up-phosphorylated Upon Hbv Infecti...supporting

confidence: 87%

Deciphering the phospho-signature induced by hepatitis B virus in primary human hepatocytes

Pastor,

Charles,

Belmudes

et al. 2024

Preprint

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“…Our previous studies have demonstrated that RBM24 can accumulate with RBM38, bind to the Pol‐ε complex, and subsequently modulate the destiny of pgRNA. RBM24 inhibits the translation of HBc on one hand and enhances the stability of HBV RNAs and promotes pgRNA packaging on the other, which subsequently suppresses HBV replication following RBM24 overexpression in vitro 17,18,32 . These findings indicated that RBM24 plays a key role in HBV replication, and an increase in the intracellular levels of RBM24 may impair HBV replication.…”

Section: Discussionmentioning

confidence: 85%

RNA‐binding motif protein 24 inhibits HBV replication in vivo

Yao

Chen

Huang

et al. 2023

Journal of Medical Virology

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Despite the extensive use of effective vaccines and antiviral drugs, chronic hepatitis B virus (HBV) infection continues to pose a serious threat to global public health. Therapies with novel mechanisms of action against HBV are being explored for achieving a functional cure. In this study, five murine models of HBV replication were used to investigate the inhibitory effect of RNA binding motif protein 24 (RBM24) on HBV replication. The findings revealed that RBM24 serves as a host restriction factor and suppresses HBV replication in vivo. The transient overexpression of RBM24 in hydrodynamics‐based mouse models of HBV replication driven by the CMV or HBV promoters suppressed HBV replication. Additionally, the ectopic expression of RBM24 decreased viral accumulation and the levels of HBV covalently closed circular DNA (cccDNA) in an rcccDNA mouse model. The liver‐directed transduction of adeno‐associated viruses (AAV)‐RBM24 mediated the stable hepatic expression of RBM24 in pAAV‐HBV1.2 and HBV/tg mouse models, and markedly reduced the levels of HBV cccDNA and other viral indicators. Altogether, these findings revealed that RBM24 inhibits the replication of HBV in vivo, and RBM24 may be a potential therapeutic target for combating HBV infections.

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“…For the function of regulating virus replication, RBM24 is more like a switch than a host limiting factor. On the one hand, RBM24 inhibits the translation of HBV and HCV, and on the other hand, enhances the replication of the HBV and HCV genome ( Cao et al, 2018 ; Yao et al, 2018 , 2019 , 2022 ). Whether or not RBM24 works as switch modulates the protein translation and RNA replication during other virus infection is an opening question now.…”

Section: Discussionmentioning

confidence: 99%

RBM24 inhibits the translation of SARS-CoV-2 polyproteins by targeting the 5ʹ-untranslated region

et al. 2023

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RNA-Binding motif protein 38 (RBM38) mediates HBV pgRNA packaging into the nucleocapsid

Cited by 8 publications

References 39 publications

Deciphering the phospho-signature induced by hepatitis B virus in primary human hepatocytes

Deciphering the phospho-signature induced by hepatitis B virus in primary human hepatocytes

RNA‐binding motif protein 24 inhibits HBV replication in vivo

RBM24 inhibits the translation of SARS-CoV-2 polyproteins by targeting the 5ʹ-untranslated region

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