Evolution of Chemical Modifications: from tRNAs to Transcriptome-Wide Surveys

化学修饰的核苷酸在RNA和DNA序列中普遍存在。它们作为表观遗传和转录组学标记，以细胞历史和环境依赖的方式调节基因组DNA和RNA转录物的功能，并影响RNA结构的稳定性。trna的修饰尤其普遍，并且似乎在进化中保存得很好。然而，他们几乎没有得到系统的关注。在这里，我们建议结合专门的深度测序方法和复杂的生物信息学方法来阐明trna中化学修饰核苷酸的进化和调节变异性。进化问题将主要通过重新调查大量公开可用的小RNA-seq数据来解决。功能意义将以芽孢杆菌和酵母的温度适应为例进行研究。作为建议研究的一部分，我们将改进相关的计算工具，从读取映射和变异调用到针对特定修改的对齐读取特征的分类模式。

Chemically modified nucleotides are ubiquitous in RNA and DNA sequences. They act as epigenetic andepitranscriptomic marks modulating the function of genomic DNA and RNA transcripts in a cell history- andenvironment-dependent manner and they influence the stability of RNA structures. Modifications in tRNAsare particularly prevalent and appear to be well conserved in evolution. Nevertheless, they have received little systematic attention. Here we propose to use a combination of specialized deep sequencing approaches and sophisticated bioinformatics methods to elucidate both the evolution and the regulated variability of chemically modified nucleotides in tRNAs. Evolutionary questions will mostly be addressed by re-investigating the plethora of publicly available small RNA-seq data. Functional implications will be studied exemplarily using temperature adaptation in Bacillales and yeast. As part of the proposed research, we will improve the relevant computational tools, from read mapping and variation calling to classifying patterns of aligned reads characteristic for specific modifications.