Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis

Yang, Wen-Lan; Qiu, Weinan; Zhang, Ting; Xu, Kai; Gu, Zi-Juan; Zhou, Yu; Xu, Heng-Ji; Yang, Zhongzhou; Shen, Bin; Zhao, Yongliang; Zhou, Qi; Yang, Ying; Li, Wei; Yang, Pengyuan; Yang, Ying

doi:10.1038/s41467-023-36595-w

Cited by 17 publications

(3 citation statements)

References 68 publications

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“…Interestingly, we wondered why the decrease in mRNA m 5 C modification was correlated with a decrease in gene expression. Recent studies have shown that modifications to transcripts can affect their stability [ 33 – 36 ]. Specifically, certain RNA-binding proteins (RBPs) can recognize and bind to these modification sites, thereby affecting their translation.…”

Section: Resultsmentioning

confidence: 99%

NSUN2/YBX1 promotes the progression of breast cancer by enhancing HGH1 mRNA stability through m5C methylation

Zhang,

An,

et al. 2024

Breast Cancer Res

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Background RNA m5C methylation has been extensively implicated in the occurrence and development of tumors. As the main methyltransferase, NSUN2 plays a crucial regulatory role across diverse tumor types. However, the precise impact of NSUN2-mediated m5C modification on breast cancer (BC) remains unclear. Our study aims to elucidate the molecular mechanism underlying how NSUN2 regulates the target gene HGH1 (also known as FAM203) through m5C modification, thereby promoting BC progression. Additionally, this study targets at preliminarily clarifying the biological roles of NSUN2 and HGH1 in BC. Methods Tumor and adjacent tissues from 5 BC patients were collected, and the m5C modification target HGH1 in BC was screened through RNA sequencing (RNA-seq) and single-base resolution m5C methylation sequencing (RNA-BisSeq). Methylation RNA immunoprecipitation-qPCR (MeRIP-qPCR) and RNA-binding protein immunoprecipitation-qPCR (RIP-qPCR) confirmed that the methylation molecules NSUN2 and YBX1 specifically recognized and bound to HGH1 through m5C modification. In addition, proteomics, co-immunoprecipitation (co-IP), and Ribosome sequencing (Ribo-Seq) were used to explore the biological role of HGH1 in BC. Results As the main m5C methylation molecule, NSUN2 is abnormally overexpressed in BC and increases the overall level of RNA m5C. Knocking down NSUN2 can inhibit BC progression in vitro or in vivo. Combined RNA-seq and RNA-BisSeq analysis identified HGH1 as a potential target of abnormal m5C modifications. We clarified the mechanism by which NSUN2 regulates HGH1 expression through m5C modification, a process that involves interactions with the YBX1 protein, which collectively impacts mRNA stability and protein synthesis. Furthermore, this study is the first to reveal the binding interaction between HGH1 and the translation elongation factor EEF2, providing a comprehensive understanding of its ability to regulate transcript translation efficiency and protein synthesis in BC cells. Conclusions This study preliminarily clarifies the regulatory role of the NSUN2-YBX1-m5C-HGH1 axis from post-transcriptional modification to protein translation, revealing the key role of abnormal RNA m5C modification in BC and suggesting that HGH1 may be a new epigenetic biomarker and potential therapeutic target for BC.

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Section: Resultsmentioning

confidence: 99%

NSUN2/YBX1 promotes the progression of breast cancer by enhancing HGH1 mRNA stability through m5C methylation

Zhang,

An,

et al. 2024

Breast Cancer Res

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“…After the staining procedure, the data were acquired with the MACSQuant Analyzer 10 from Miltenyi Biotec and processed using the FlowJo software (v10.5.3). In this study, CD4 + IL-17A + cells are denoted as Th17 60 and CD4 + Foxp3 + cells are denoted as Treg. 61 …”

Section: Methodsmentioning

confidence: 99%

GSK2334470 attenuates high salt-exacerbated rheumatoid arthritis progression by restoring Th17/Treg homeostasis

Mo,

Bolideei,

Rong

et al. 2024

iScience

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“…NSUN2通过催化IL-17A mRNA C466的m 5 C修饰, 促进了IL-17A在T淋巴细胞中的翻译, 介导高同型半胱氨酸血症(hyperhomocysteinemia, HHcy)诱导T淋巴细胞活化 [149] . Nsun2与RoRγt偶联, 特异性催化Th17细胞关键细胞因子mRNA m 5 C修饰的形成, 增强其靶基因的稳定性, 诱导肠炎发生 [150] .…”

Section: 在食管鳞状细胞癌样本中转录因子E2f1可调控unclassified