PHOTOSYNTHESIS RESEARCH
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2015
·Vol. 126
·期 2
·311-321
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IF 3.502
Zhang Hong-Dao,Cui Yong-Lan,Huang Chao,Yin Qian-Qian,Qin Xue-Mei,Xu Te,He Xiao-Fang,Zhang Yi,Li Zi-Ran,Yang Zhong-Nan
After transcription, most chloroplast precursor RNAs undergo further post-transcriptional processing including cleavage, editing, and splicing. Previous investigation has shown that the cleavage of the rpoA transcript and most editing sites, including accD - 1 , are defective in the knockout mutant of PDM1/SEL1, a PLS-type PPR protein, and that PDM1 is associated with the rpoA transcript. In this work, we found that the splicing of group II introns in trnK and ndhA is also affected in pdm1 . Co-immunoprecipitation mass spectrometry experiments were performed to identify proteins that are associated with PDM1. We obtained 126 non-redundant proteins, of which MORF9 was reported to be involved in RNA editing in chloroplast. Yeast two-hybrid assays showed that PDM1 interacts directly with MORF9, MORF2, and MORF8. RNA immunoprecipitation showed that PDM1 associates with the transcripts of trnK and ndhA , as well as accD - 1, suggesting that PDM1 is involved in RNA editing and splicing. Therefore, PDM1 is an important protein for post-transcriptional regulation in chloroplast.
研究领域:
植物学
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分子生物学
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DOI
PubMed
高影响因子
IMMUNITY
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2024
·
IF 25.5
Rui Ding,Xiaoyan Yu,Zhilin Hu,Yu Dong,Haiyan Huang,Yuerong Zhang,Qiaoqiao Han,Zhi-Yu Ni,Ren Zhao,Youqiong Ye,Qiang Zou
RNA splicing is involved in cancer initiation and progression, but how it influences host antitumor immunity in the metabolically abnormal tumor microenvironment (TME) remains unclear. Here, we demonstrate that lactate modulates Foxp3-dependent RNA splicing to maintain the phenotypic and functional status of tumor-infiltrating regulatory T (Treg) cells via CTLA-4. RNA splicing in Treg cells was correlated with the Treg cell signatures in the TME. Ubiquitin-specific peptidase 39 (USP39), a component of the RNA splicing machinery, maintained RNA-splicing-mediated CTLA-4 expression to control Treg cell function. Mechanistically, lactate promoted USP39-mediated RNA splicing to facilitate CTLA-4 expression in a Foxp3-dependent manner. Moreover, the efficiency of CTLA-4 RNA splicing was increased in tumor-infiltrating Treg cells from patients with colorectal cancer. These findings highlight the immunological relevance of RNA splicing in Treg cells and provide important insights into the environmental mechanism governing CTLA-4 expression in Treg cells.
研究领域:
免疫学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Genetics
·
2021
·
IF 4.599
Yang Hong,Wu Yi-Fan,Ding Jie,Liu Wei,Zhu De-Sheng,Shen Xia-Feng,Guan Yang-Tai
Background: N6-Methyladenosine (m6A) methylation is the most prevalent internal posttranscriptional modification on mammalian mRNA. But its role in neuromyelitis optica spectrum disorders (NMOSD) is not known.Aims: To explore the mechanism of m6A in NMOSD patients.Methods: This study assessed the m6A methylation levels in blood from two groups: NMOSD patients and healthy controls. Methylated RNA immunoprecipitation Sequencing (MeRIP-seq) and RNA-seq were performed to assess differences in m6A methylation between NMOSD patients and healthy controls. Ultra-high performance liquid chromatography coupled with triple quadruple mass spectrometry (UPLC-QQQ-MS) method was performed to check m6A level. Differential m6A methylation genes were validated by MeRIP-qPCR.Results: Compared with that in the control group, the total m6A level was decreased in the NMOSD group. Genes with upregulated methylation were primarily enriched in processes associated with RNA splicing, mRNA processing, and innate immune response, while genes with downregulated methylation were enriched in processes associated with the regulation of transcription, DNA-templating, and the positive regulation of I-kappa B kinase/NF-kappa B signalling.Conclusion: These findings demonstrate that differential m6A methylation may act on functional genes to regulate immune homeostasis in NMOSD.
研究领域:
神经病学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-23
·
IF 14.7
Luo Yu-Wei,Zhou Jiang-Peng,Ji Hongyu,Xu Doudou,Zheng Anqi,Wang Xin,Dai Zhizheng,Luo Zhicheng,Cao Fang,Wang Xing-Yue,Bai Yunfang,Chen Di,Chen Yueming,Wang Qi,Yang Yaying,Zhang Xinghai,Chiu Sandra,Peng Xiaozhong,Huang Ai-Long,Tang Kai-Fu
Though RNAi and RNA-splicing machineries are involved in regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, their precise roles in coronavirus disease 2019 (COVID-19) pathogenesis remain unclear. Herein, we show that decreased RNAi component (Dicer and XPO5) and splicing factor (SRSF3 and hnRNPA3) expression correlate with increased COVID-19 severity. SARS-CoV-2 N protein induces the autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inhibiting miRNA biogenesis and RNA splicing and triggering DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 knockdown increases, while their overexpression decreases, N protein-induced pneumonia’s severity. Older mice show lower expression of Dicer, XPO5, SRSF3, and hnRNPA3 in their lung tissues and exhibit more severe N protein-induced pneumonia than younger mice. PJ34, a poly(ADP-ribose) polymerase inhibitor, or anastrozole, an aromatase inhibitor, ameliorates N protein- or SARS-CoV-2-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.
研究领域:
分子生物学
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病毒学
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免疫学
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药理学
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病理学
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产品关联
DOI
PubMed
高影响因子
Cell Chemical Biology
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2024
·
IF 6.6
KeJing Zhang,Juan Wei,SheYu Zhang,Liyan Fei,Lu Guo,Xueying Liu,YiShuai Ji,WenJun Chen,Felipe E. Ciamponi,WeiChang Chen,MengXi Li,Jie Zhai,Ting Fu,Katlin B. Massirer,Yang Yu,Mathieu Lupien,Yong Wei,Cheryl. H. Arrowsmith,Qin Wu,WeiHong Tan
Paclitaxel-resistant triple negative breast cancer (TNBC) remains one of the most challenging breast cancers to treat. Here, using an epigenetic chemical probe screen, we uncover an acquired vulnerability of paclitaxel-resistant TNBC cells to protein arginine methyltransferases (PRMTs) inhibition. Analysis of cell lines and in-house clinical samples demonstrates that resistant cells evade paclitaxel killing through stabilizing mitotic chromatin assembly. Genetic or pharmacologic inhibition of PRMT5 alters RNA splicing, particularly intron retention of aurora kinases B (AURKB), leading to a decrease in protein expression, and finally results in selective mitosis catastrophe in paclitaxel-resistant cells. In addition, type I PRMT inhibition synergies with PRMT5 inhibition in suppressing tumor growth of drug-resistant cells through augmenting perturbation of AURKB-mediated mitotic signaling pathway. These findings are fully recapitulated in a patient-derived xenograft (PDX) model generated from a paclitaxel-resistant TNBC patient, providing the rationale for targeting PRMTs in paclitaxel-resistant TNBC.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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药理学
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产品关联
DOI
PubMed
高影响因子
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