簡介:
- 作者: Min Ni, Bingbing Li, Lingli Wang, Shengju Ma, Kun Ma
- 雜志: Virology Journal
- Doi: https://www.doi.org/10.1186/s12985-025-03008-x
- 出版日期: 2025/12/22
摘要
Background
Hepatitis B virus (HBV) is a major human pathogen and chronically infects over 250 million people globally. The objective of our study is to investigate the mechanism of RBM15 in HBV replication, providing novel targets for HB treatment.
Methods
Huh-7 cells were treated with pHBV1.3. pHBV1.3 replication in Huh-7 cells was verified by detection of HBV RNAs, HBV pgRNA and HBx levels. The expression of RBM15, HULC and BRD4 was detected by qRT-PCR or WB. After RBM15 intervention, the effect of RBM15 on HBV replication was evaluated by detections of HBV DNA and HBV RNAs via q-PCR or qRT-PCR, HBsAg and HBeAg through ELISA. Total m6A levels were analyzed by m6A quantification. The m6A enrichment on HULC was analyzed by MeRIP. Bindings of HULC to ELAVL1, and ELAVL1 to BRD4 mRNA were examined by RIP. BRD4 stability was evaluated following actinomycin D treatment. HULC or BRD4 overexpression was combined with RBM15 inhibition to validate the mechanism. Finally, the HBV replication mouse model was established for mechanism verification.
Results
RBM15 was overexpressed during HBV replication. RBM15 inhibition suppressed HBV replication. RBM15 enhanced the m6A modification on HULC and stabilized HULC expression. HULC bound to ELAVL1 and elevated BRD4 protein expression. HULC or BRD4 overexpression partially reversed the inhibitory effect of RBM15 on HBV replication.
Conclusions
RBM15 enhances HBV replication by promoting the binding of HULC to ELAVL1 through m6A modification, and increasing BRD4 expression.
關于派真
作為一家專注于AAV 技術十余年，深耕基因治療領域的CRO&CDMO，派真生物可提供從載體設計、構建到 AAV、慢病毒和 mRNA 服務的一站式解決方案。憑借深厚的技術實力、卓越的運營管理和高標準的服務交付，我們為全球客戶提供一站式CMC解決方案，包括從早期概念驗證、成藥性評估到IIT、IND及BLA的各個階段。
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憑借我們獨立知識產權的π-alphaTM 293 細胞AAV高產技術平臺，我們能將AAV產量提高多至10倍，每批次產量可達1×101?vg，以滿足多樣化的商業化和臨床項目需求。此外，我們定制化的mRNA和脂質納米顆粒（LNP）產品及服務覆蓋藥物和疫苗開發的各個階段，從研發到符合GMP的生產，提供端到端的一站式解決方案。
