FTSJ3

Last update 23 Jan 2025

Basic Info

Synonyms

FtsJ RNA 2'-O-methyltransferase 3, FTSJ3, pre-rRNA 2'-O-ribose RNA methyltransferase FTSJ3

+ [3]

Introduction

RNA 2'-O-methyltransferase involved in the processing of the 34S pre-rRNA to 18S rRNA and in 40S ribosomal subunit formation. (Microbial infection) In case of infection by HIV-1 virus, recruited to HIV-1 RNA and catalyzes 2'-O-methylation of the viral genome, allowing HIV-1 virus to escape the innate immune system (PubMed:30626973). RNA 2'-O-methylation provides a molecular signature for discrimination of self from non-self and is used by HIV-1 to evade innate immune recognition by IFIH1/MDA5 (PubMed:30626973). Mediates methylation of internal residues of HIV-1 RNA, with a strong preference for adenosine (PubMed:30626973). Recruited to HIV-1 RNA via interaction with TARBP2/TRBP (PubMed:30626973).

100 Clinical Results associated with FTSJ3

100 Translational Medicine associated with FTSJ3

0 Patents (Medical) associated with FTSJ3

Literatures (Medical) associated with FTSJ3

01 May 2024·médecine/sciences

Effets de la 2′-O-méthylation de l’ARN génomique du VIH-1 sur la réplication virale

Review

Author: Decroly, Étienne ; El-Kazzi, Priscila ; Decombe, Alice ; Nisole, Sébastien

09 Feb 2024·Nucleic Acids Research

Internal RNA 2′-O-methylation on the HIV-1 genome impairs reverse transcription

Article

Author: Sutto-Ortiz, Priscila ; Decombe, Alice ; Piorkowski, Géraldine ; Chamontin, Célia ; Canard, Bruno ; Peersen, Olve ; Decroly, Etienne ; Nisole, Sébastien

AbstractViral RNA genomes are modified by epitranscriptomic marks, including 2′-O-methylation that is added by cellular or viral methyltransferases. 2′-O-Methylation modulates RNA structure, function and discrimination between self- and non-self-RNA by innate immune sensors such as RIG-I-like receptors. This is illustrated by human immunodeficiency virus type-1 (HIV-1) that decorates its RNA genome through hijacking the cellular FTSJ3 2′-O-methyltransferase, thereby limiting immune sensing and interferon production. However, the impact of such an RNA modification during viral genome replication is poorly understood. Here we show by performing endogenous reverse transcription on methylated or hypomethylated HIV-1 particles, that 2′-O-methylation negatively affects HIV-1 reverse transcriptase activity. Biochemical assays confirm that RNA 2′-O-methylation impedes reverse transcriptase activity, especially at low dNTP concentrations reflecting those in quiescent cells, by reducing nucleotide incorporation efficiency and impairing translocation. Mutagenesis highlights K70 as a critical amino acid for the reverse transcriptase to bypass 2′-O-methylation. Hence, the observed antiviral effect due to viral RNA 2′-O-methylation antagonizes the FTSJ3-mediated proviral effects, suggesting the fine-tuning of RNA methylation during viral replication.

01 Feb 2024·Cancer Research

RNA Methyltransferase FTSJ3 Regulates the Type I Interferon Pathway to Promote Hepatocellular Carcinoma Immune Evasion

Article

Author: Zhang, Yindan ; Wang, Yingchao ; Zeng, Yongyi ; Zhuang, Qiuyu ; Liu, Xiaolong ; Bai, Shaoyi ; Zheng, Youshi ; Guo, Wuhua ; Zhao, Bixing ; Xu, Xuechun ; Dai, Zhiguo ; Hu, En ; Xing, Xiaohua

AbstractImmunotherapies such as immune checkpoint blockade have achieved remarkable success in treating cancer. Unfortunately, response rates have been limited in multiple cancers including hepatocellular carcinoma (HCC). The critical function of epigenetics in tumor immune evasion and antitumor immunity supports harnessing epigenetic regulators as a potential strategy to enhance the efficacy of immunotherapy. Here, we discovered a tumor-promoting function of FTSJ3, an RNA 2′-O-methyltransferase, in HCC by suppressing antitumor immune responses. FTSJ3 was upregulated in hepatocellular carcinoma, and high FTSJ3 expression correlated with reduced patient survival. Deletion of FTSJ3 blocked HCC growth and induced robust antitumor immune responses. Mechanistically, FTSJ3 suppressed double-stranded RNA (dsRNA)–induced IFNβ signaling in a 2′-O-methyltransferase manner. Deletion of RNA sensors in HCC cells or systemic knockout of type I IFN receptor IFNAR in mice rescued the in vivo tumor growth defect caused by FTSJ3 deficiency, indicating that FTSJ3 deletion suppresses tumor growth by activating the RNA sensor–mediated type I IFN pathway. Furthermore, FTSJ3 deletion significantly enhanced the efficacy of programmed cell death protein 1 (PD-1) immune checkpoint blockade. The combination of FTSJ3 deficiency and anti–PD-1 antibody treatment effectively eradicated tumors and increased the survival time. In conclusion, this study reveals an epigenetic mechanism of tumor immune evasion and, importantly, suggests FTSJ3-targeting therapies as potential approach to overcome immunotherapy resistance in patients with HCC.Significance:Hepatocellular carcinoma cells use 2′-O-methylation catalyzed by FTSJ3 for immune evasion by suppressing abnormal dsRNA-mediated type I IFN responses, providing a potential target to activate antitumor immunity and enhance immunotherapy efficacy.

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FTSJ3

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