Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
RNA. 2024 Jul 16;30(8):1025-1040. doi: 10.1261/rna.080004.124.
RNA modifications have a substantial impact on tRNA function, with modifications in the anticodon loop contributing to translational fidelity and modifications in the tRNA core impacting structural stability. In bacteria, tRNA modifications are crucial for responding to stress and regulating the expression of virulence factors. Although tRNA modifications are well-characterized in a few model organisms, our knowledge of tRNA modifications in human pathogens, such as , remains limited. Here, we leveraged two orthogonal approaches to build a reference landscape of tRNA modifications in , which enabled us to identify similar modifications in Our analysis supports a substantial degree of conservation between the two organisms, while also uncovering potential sites of tRNA modification in tRNAs that are not present in The mutational signature at one of these sites, position 46 of tRNA is dependent on the homolog of TapT, the enzyme responsible for the 3-(3-amino-3-carboxypropyl) uridine (acpU) modification. Identifying which modifications are present on different tRNAs will uncover the pathways impacted by the different tRNA-modifying enzymes, some of which play roles in determining virulence and pathogenicity.
RNA 修饰对 tRNA 功能有重大影响,反密码环中的修饰有助于提高翻译保真度,tRNA 核心中的修饰则影响结构稳定性。在细菌中,tRNA 修饰对于应对压力和调节毒力因子的表达至关重要。尽管在少数模式生物中已经对 tRNA 修饰进行了很好的研究,但我们对人类病原体(如 )中的 tRNA 修饰的了解仍然有限。在这里,我们利用两种正交方法构建了 在 中的 tRNA 修饰参考图谱,这使我们能够在 中识别出相似的修饰。我们的分析支持这两个生物体之间存在很大程度的保守性,同时也揭示了 在 中不存在的 tRNA 修饰的潜在位点。这些位点之一,tRNA 的 46 位的突变特征依赖于 TapT 的 同源物,TapT 是负责 3-(3-氨基-3-羧基丙基)尿嘧啶 (acpU) 修饰的酶。确定不同 tRNA 上存在哪些修饰将揭示受不同 tRNA 修饰酶影响的途径,其中一些酶在决定毒力和致病性方面发挥作用。