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Co-regulatory crosstalk between m5C, m7G, and o8G RNA modifications via QKI/YBX1 axis in myocardial ischemia-reperfusion injury 心肌缺血-再灌注损伤中m5C、m7G和o8G RNA修饰通过QKI/YBX1轴的共调控串扰
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-04 DOI: 10.1016/j.ygeno.2026.111193
Ziqiang Yang , Suyun Chen , Siman Shen , Wanglong Liu , Kun Ding , Fangni Cao , Simeng Li , Minjuan Zeng , Jianning Chen , Li Xu , Liangqing Zhang

Background

Ischemia–reperfusion (I/R) injury in the heart triggers oxidative stress and alters post-transcriptional gene regulation. Reactive oxygen species (ROS) generated during oxidative stress induce RNA modifications such as 8-oxo-guanosine (o8G). Other modifications including 5-methylcytosine (m5C) and 7-methylguanosine (m7G) may also contribute to cardiac dysfunction. While the roles of individual RNA modifications in I/R injury are increasingly recognized, the global dynamics and crosstalk among these modifications under oxidative stress remain largely unexplored.

Methods

We performed high-throughput sequencing specific to each modification, integrated with mRNA transcriptome profiling of an IR injury mouse model. Differentially modified transcripts were subjected to GO and KEGG enrichment analyses to elucidate their functional relevance. Mechanistically, we demonstrated that RNA modification regulators with distinct functional roles can physically interact with each other, as shown by co-immunoprecipitation and immunofluorescence assays. Global changes in RNA modification levels under the model conditions were assessed using dot blot analysis. Furthermore, the regulatory effects of these enzymes on target mRNA stability were evaluated via Actinomycin D transcriptional inhibition assays.

Results

We found that the levels of all three modifications, m5C, m7G, and o8G were increased in IR by dot blot and observed a significant upregulation of three modification peaks under I/R by MeRIP-seq. Both m5C and o8G were predominantly enriched in CDS, while m7G displayed a dynamic redistribution. Our study focuses on the co-regulation crosstalk among three modifications. Functionally, singly or combinatorially modified transcripts were enriched in actin cytoskeleton regulation. Mechanistically, the transcripts of the regulators can be modified by each other and QKI can modulate the global modification level of o8G. QKI and YBX1 interact with each other to cooperatively stabilize ACTN4 mRNA, thereby maintaining cytoskeletal integrity.

Conclusion

Our results establish that QKI and YBX1 modulate the actin cytoskeleton via a coordinated network of m5C, m7G, and o8G in I/R injury.
背景:心脏缺血再灌注(I/R)损伤触发氧化应激并改变转录后基因调控。氧化应激过程中产生的活性氧(ROS)可诱导RNA修饰,如8-氧鸟苷(o8G)。其他修饰包括5-甲基胞嘧啶(m5C)和7-甲基鸟苷(m7G)也可能导致心功能障碍。虽然个体RNA修饰在I/R损伤中的作用越来越被认识到,但氧化应激下这些修饰之间的全局动态和相互作用在很大程度上仍未被探索。方法:我们对每种修饰进行了高通量测序,并结合了IR损伤小鼠模型的mRNA转录组分析。差异修饰转录本进行GO和KEGG富集分析,以阐明其功能相关性。在机制上,我们证明了具有不同功能作用的RNA修饰调节剂可以相互作用,正如免疫共沉淀和免疫荧光实验所显示的那样。在模型条件下,RNA修饰水平的整体变化使用点印迹分析进行评估。此外,通过放线菌素D转录抑制实验评估这些酶对靶mRNA稳定性的调节作用。结果:我们发现m5C、m7G和o8G这三种修饰的水平在IR中都增加了,并且通过MeRIP-seq观察到I/R下三个修饰峰的显著上调。m5C和o8G主要富集于CDS,而m7G则表现为动态再分布。我们的研究重点是三种修饰之间的共调节串扰。功能上,单个或组合修饰的转录本在肌动蛋白细胞骨架调控中富集。从机制上讲,调控因子的转录本可以相互修饰,QKI可以调节o8G的全局修饰水平。QKI和YBX1相互作用,共同稳定ACTN4 mRNA,从而维持细胞骨架的完整性。结论:在I/R损伤中,QKI和YBX1通过m5C、m7G和o8G的协同网络调节肌动蛋白细胞骨架。
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引用次数: 0
Mechanism of lead resistance in Wickerhamomyces anomalus: Insights from whole genome sequencing 异常柳杉耐铅机制:来自全基因组测序的见解。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-03 DOI: 10.1016/j.ygeno.2025.111192
Lijie Li, Ganqiqige Cha, Fengsheng Zhang
Lead contamination in air, water, and soil has infiltrated foods and feeds, posing severe health risks to humans and animals and remaining a tough challenge. Yeast is a safe and efficient biosorbent for lead removal. This study explored W. anomalus QF-11 lead resistance via whole-genome sequencing, finding it tolerates up to 7000 mg/L Pb2+. Under 4000 mg/L Pb2+ stress, it enhances resistance by scavenging ROS, increasing soluble protein, boosting SOD, POD and CAT activities, and elevating glutathione and trehalose levels. Its genome annotates 63 ABC transporters and antioxidant genes involved in lead adsorption, transportation and compartmentalization, with SODC, SODM, VAN1, TSL1 and others significantly upregulated. This study provides a theoretical basis for W. anomalus QF-11 application as a Pb2+ biosorbent and data support for novel heavy metal adsorbent development.
空气、水和土壤中的铅污染已经渗透到食品和饲料中,对人类和动物构成严重的健康风险,这仍然是一项艰巨的挑战。酵母是一种安全有效的生物吸附剂。本研究通过全基因组测序研究了W. anomalus QF-11对铅的抗性,发现其耐受高达7000 mg/L的Pb2+。在4000 mg/L Pb2+胁迫下,通过清除活性氧,增加可溶性蛋白,提高SOD、POD和CAT活性,提高谷胱甘肽和海藻糖水平来增强抗性。其基因组注释了63个参与铅吸附、运输和区室化的ABC转运蛋白和抗氧化基因,其中SODC、SODM、VAN1、TSL1等显著上调。该研究为W. anomalus QF-11作为Pb2+生物吸附剂的应用提供了理论基础,并为新型重金属吸附剂的开发提供了数据支持。
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引用次数: 0
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
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