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不同血细胞群体中tRNA衍生片段库的变化

Changes in the Repertoire of tRNA-Derived Fragments in Different Blood Cell Populations.

作者信息

Artamonov Alexander A, Kondratov Kirill A, Bystritsky Egor A, Nikitin Yuri V, Velmiskina Anastasiya A, Mosenko Sergey V, Polkovnikova Irina A, Asinovskaya Anna Yu, Apalko Svetlana V, Sushentseva Natalya N, Ivanov Andrey M, Scherbak Sergey G

机构信息

City Hospital No. 40, St. Petersburg 197706, Russia.

Kirov Military Medical Academy, St. Petersburg 194044, Russia.

出版信息

Life (Basel). 2024 Oct 12;14(10):1294. doi: 10.3390/life14101294.

DOI:10.3390/life14101294
PMID:39459595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11509557/
Abstract

tRNA-derived fragments function as markers in addition to playing the key role of signalling molecules in a number of disorders. It is known that the repertoire of these molecules differs greatly in different cell types and varies depending on the physiological condition. The aim of our research was to compare the pattern of tRF expression in the main blood cell types and to determine how the composition of these molecules changes during COVID-19-induced cytokine storms. Erythrocytes, monocytes, lymphocytes, neutrophils, basophils and eosinophils from control donors and patients with severe COVID-19 were obtained by fluorescence sorting. We extracted RNA from FACS-sorted cells and performed NGS of short RNAs. The composition of tRNA-derived fragments was analysed by applying a semi-custom bioinformatic pipeline. In this study, we assessed the length and type distribution of tRFs and reported the 150 most prevalent tRF sequences across all cell types. Additionally, we demonstrated a significant ( < 0.05, fold change >16) change in the pattern of tRFs in erythrocytes (21 downregulated, 12 upregulated), monocytes (53 downregulated, 38 upregulated) and lymphocytes (49 upregulated) in patients with severe COVID-19. Thus, different blood cell types exhibit a significant variety of tRFs and react to the cytokine storm by dramatically changing their differential expression patterns. We suppose that the observed phenomenon occurs due to the regulation of nucleotide modifications and alterations in activity of various Rnases.

摘要

tRNA衍生片段除了在多种疾病中发挥信号分子的关键作用外,还可作为标志物。已知这些分子在不同细胞类型中的种类差异很大,并随生理状态而变化。我们研究的目的是比较主要血细胞类型中tRF的表达模式,并确定在新冠病毒诱导的细胞因子风暴期间这些分子的组成如何变化。通过荧光分选从对照供体和重症新冠患者中获取红细胞、单核细胞、淋巴细胞、中性粒细胞、嗜碱性粒细胞和嗜酸性粒细胞。我们从FACS分选的细胞中提取RNA,并对短RNA进行了NGS。通过应用半定制生物信息学流程分析了tRNA衍生片段的组成。在本研究中,我们评估了tRF的长度和类型分布,并报告了所有细胞类型中最普遍的150个tRF序列。此外,我们证明了重症新冠患者红细胞(21个下调,12个上调)、单核细胞(53个下调,38个上调)和淋巴细胞(49个上调)中tRF模式存在显著变化(<0.05,变化倍数>16)。因此,不同血细胞类型表现出显著多样的tRF,并通过显著改变其差异表达模式对细胞因子风暴做出反应。我们推测观察到的现象是由于核苷酸修饰的调节和各种核糖核酸酶活性的改变所致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f54/11509557/3184f6383ebc/life-14-01294-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f54/11509557/e69be596c28f/life-14-01294-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f54/11509557/ee0f884a038b/life-14-01294-g005a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f54/11509557/d3f88f358f27/life-14-01294-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f54/11509557/d5ab3c0cc892/life-14-01294-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f54/11509557/3184f6383ebc/life-14-01294-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f54/11509557/e69be596c28f/life-14-01294-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f54/11509557/ea4961c28259/life-14-01294-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f54/11509557/735b396a0c9a/life-14-01294-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f54/11509557/3aaf1c7552cf/life-14-01294-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f54/11509557/ee0f884a038b/life-14-01294-g005a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f54/11509557/d3f88f358f27/life-14-01294-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f54/11509557/d5ab3c0cc892/life-14-01294-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f54/11509557/3184f6383ebc/life-14-01294-g008.jpg

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本文引用的文献

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The role and mechanism of action of tRNA-derived fragments in the diagnosis and treatment of malignant tumors.tRNA 衍生片段在恶性肿瘤诊断和治疗中的作用及机制。
Cell Commun Signal. 2023 Mar 24;21(1):62. doi: 10.1186/s12964-023-01079-3.
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Emerging roles of tRNA-derived fragments in cancer.
tRNA 衍生片段在癌症中的新兴作用。
Mol Cancer. 2023 Feb 13;22(1):30. doi: 10.1186/s12943-023-01739-5.
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tRNA derived fragments:A novel player in gene regulation and applications in cancer.转运RNA衍生片段:基因调控中的新角色及其在癌症中的应用
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