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
City Hospital No. 40, St. Petersburg 197706, Russia.
Kirov Military Medical Academy, St. Petersburg 194044, Russia.
Life (Basel). 2024 Oct 12;14(10):1294. doi: 10.3390/life14101294.
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.
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。