Shigematsu Megumi, Matsubara Ryuma, Gumas Justin, Kawamura Takuya, Kirino Yohei
Computational Medicine Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Department of Biochemistry and Molecular Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Biosci Biotechnol Biochem. 2025 Feb 20;89(3):398-405. doi: 10.1093/bbb/zbae192.
Angiogenin (Ang), an endoribonuclease belonging to the RNase A superfamily, cleaves the anticodon-loops of tRNAs to produce tRNA-half molecules. Although previous studies have demonstrated the involvement of Ang in the pathobiology of neurodegenerative disorders, the characterization of Ang-generated tRNA halves in neuronal cells remains limited. This is partly due to the technical limitations of standard RNA-seq methods, which cannot capture Ang-generated RNAs containing a 2',3'-cyclic phosphate (cP). In this report, we established an Ang-treatment model using SH-SY5Y, a human neuroblastoma cell line, and demonstrated Ang-dependent accumulation of tRNA halves. By performing cP-RNA-seq, which selectively captures cP-containing RNAs, we identified Ang-generated tRNA halves and the specific cleavage positions within tRNA anticodon-loops responsible for their generation. Our results provide insights into the anticodon-loop cleavage and the selective production of a specific subset of tRNA halves by Ang.
血管生成素（Ang）是一种属于核糖核酸酶A超家族的核糖核酸内切酶，它切割tRNA的反密码子环以产生tRNA半分子。尽管先前的研究已经证明Ang参与神经退行性疾病的病理生物学过程，但在神经元细胞中由Ang产生的tRNA半分子的特征仍很有限。部分原因是标准RNA测序方法的技术局限性，该方法无法捕获含有2'，3'-环磷酸酯（cP）的由Ang产生的RNA。在本报告中，我们使用人神经母细胞瘤细胞系SH-SY5Y建立了Ang处理模型，并证明了tRNA半分子的Ang依赖性积累。通过进行选择性捕获含cP RNA的cP-RNA测序，我们鉴定了由Ang产生的tRNA半分子以及tRNA反密码子环内负责其产生的特定切割位置。我们的结果为Ang对反密码子环的切割以及特定tRNA半分子子集的选择性产生提供了见解。
