Oberbauer Vera, Schaefer Matthias R
Division of Cell and Developmental Biology, Center for Anatomy and Cell Biology, Medical University Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria.
Genes (Basel). 2018 Dec 5;9(12):607. doi: 10.3390/genes9120607.
Transfer RNAs (tRNAs) are abundant small non-coding RNAs that are crucially important for decoding genetic information. Besides fulfilling canonical roles as adaptor molecules during protein synthesis, tRNAs are also the source of a heterogeneous class of small RNAs, tRNA-derived small RNAs (tsRNAs). Occurrence and the relatively high abundance of tsRNAs has been noted in many high-throughput sequencing data sets, leading to largely correlative assumptions about their potential as biologically active entities. tRNAs are also the most modified RNAs in any cell type. Mutations in tRNA biogenesis factors including tRNA modification enzymes correlate with a variety of human disease syndromes. However, whether it is the lack of tRNAs or the activity of functionally relevant tsRNAs that are causative for human disease development remains to be elucidated. Here, we review the current knowledge in regard to tsRNAs biogenesis, including the impact of RNA modifications on tRNA stability and discuss the existing experimental evidence in support for the seemingly large functional spectrum being proposed for tsRNAs. We also argue that improved methodology allowing exact quantification and specific manipulation of tsRNAs will be necessary before developing these small RNAs into diagnostic biomarkers and when aiming to harness them for therapeutic purposes.
转运RNA（tRNA）是丰富的小非编码RNA，对解码遗传信息至关重要。除了在蛋白质合成过程中作为衔接分子发挥经典作用外，tRNA也是一类异质性小RNA——tRNA衍生小RNA（tsRNA）的来源。在许多高通量测序数据集中都已注意到tsRNA的存在及其相对较高的丰度，这导致人们对其作为生物活性实体的潜力大多是基于相关性的假设。tRNA也是任何细胞类型中修饰最多的RNA。包括tRNA修饰酶在内的tRNA生物合成因子的突变与多种人类疾病综合征相关。然而，究竟是tRNA的缺乏还是功能相关tsRNA的活性导致人类疾病的发展仍有待阐明。在此，我们综述了目前关于tsRNA生物合成的知识，包括RNA修饰对tRNA稳定性的影响，并讨论了支持tsRNA所提出的看似广泛的功能谱的现有实验证据。我们还认为，在将这些小RNA开发成诊断生物标志物以及旨在将它们用于治疗目的之前，需要改进方法以实现对tsRNA的精确量化和特异性操作。
