通讯作者: 高国生, 495926922@qq.com

DOI：10.12201/bmr.202605.00065

Research Progress of Splicing Factor SART1 in Viral Infection and Immune Regulation

• 摘要：SART1（squamous cell carcinoma antigen recognized by T cells 1）最初作为肿瘤排斥抗原被发现，随后被证实是U4/U6.U5 tri-snRNP复合物的重要组成部分，在前体mRNA（pre-mRNA）剪接过程中发挥关键作用。近年来研究表明，SART1不仅参与经典RNA剪接调控，还广泛介导病毒感染、宿主抗病毒免疫、缺氧应答、DNA损伤修复及肿瘤免疫调控等多种生物学过程，表现出显著的多功能性。在病毒感染中，SART1作为重要的宿主限制因子和干扰素效应基因（interferon effector gene，IEG），可通过调控干扰素刺激基因（interferon-stimulated genes，ISGs）表达及宿主转录网络抑制乙型肝炎病毒（hepatitis B virus，HBV）和丙型肝炎病毒（hepatitis C virus，HCV）复制。其中，SART1可通过抑制肝细胞核因子4α（hepatocyte nuclear factor 4α，HNF4α）转录，下调HBV共价闭合环状DNA（covalently closed circular DNA，cccDNA）活性，从而显著抑制病毒复制；其基础表达水平还与慢性HBV患者干扰素-α（interferon-α，IFN-α）治疗应答密切相关，提示其具有潜在的疗效预测价值。在肿瘤免疫方面，SART1编码的抗原肽可诱导HLA-A24/A26限制性细胞毒性T淋巴细胞（cytotoxic T lymphocyte，CTL）反应，并已应用于树突状细胞（dendritic cell，DC）疫苗和mRNA疫苗研究。此外，SART1还可通过调控巨噬细胞极化及NF-κB信号通路参与免疫微环境重塑和代谢功能障碍相关脂肪性肝炎（metabolic dysfunction-associated steatohepatitis，MASH）向肝细胞癌（hepatocellular carcinoma，HCC）的进展。本文系统综述SART1的结构特征、分子功能、病毒感染中的作用机制、肿瘤免疫功能及临床转化前景，并探讨其在“剪接—代谢—免疫”交互网络中的关键作用，以期为慢性持续性感染及相关恶性肿瘤的联合干预提供新的理论依据和潜在治疗靶点。

  关键词： SART1; 病毒; 干扰素; 肿瘤排斥抗原; 免疫调控

   

  Abstract: SART1 (squamous cell carcinoma antigen recognized by T cells 1) was initially discovered as a tumor rejection antigen and later confirmed to be a crucial component of the U4/U6.U5 tri-snRNP complex, playing a key role in precursor mRNA (pre-mRNA) splicing. Recent studies indicate that SART1 is not only involved in canonical RNA splicing regulation but also broadly mediates diverse biological processes, including viral infection, host antiviral immunity, hypoxia response, DNA damage repair, and tumor immune regulation, demonstrating significant functional versatility. In the context of viral infection, SART1 acts as an important host restriction factor and an interferon effector gene (IEG), capable of inhibiting the replication of hepatitis B virus (HBV) and hepatitis C virus (HCV) by regulating the expression of interferon-stimulated genes (ISGs) and the host transcriptional network. Specifically, SART1 can significantly suppress HBV replication by inhibiting hepatocyte nuclear factor 4α (HNF4α) transcription, thereby downregulating the activity of HBV covalently closed circular DNA (cccDNA). Its baseline expression level is also closely associated with the interferon-α (IFN-α) treatment response in chronic HBV patients, suggesting its potential value for predicting therapeutic efficacy. Regarding tumor immunity, antigenic peptides encoded by SART1 can induce HLA-A24/A26-restricted cytotoxic T lymphocyte (CTL) responses and have been applied in dendritic cell (DC) vaccine and mRNA vaccine research. Additionally, SART1 is involved in reshaping the immune microenvironment and the progression from metabolic dysfunction-associated steatohepatitis (MASH) to hepatocellular carcinoma (HCC) by regulating macrophage polarization and the NF-κB signaling pathway. This article systematically reviews the structural characteristics, molecular functions, mechanisms of action in viral infection, roles in tumor immunity, and clinical translational prospects of SART1. It also explores its pivotal role within the splicing–metabolism–immunity interaction network, aiming to provide a new theoretical basis and potential therapeutic targets for the combined intervention of chronic persistent infections and associated malignant tumors.

  Key words: SART1; virus; interferon; tumor rejection antigen; immune regulation

  提交时间：2026-05-18

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• 序号	提交日期	编号	操作
  1	2026-04-29	10.12201/bmr.202605.00065V1	下载

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