Department of Biological Sciences, Xi'an Jiaotong-Liverpool University, Suzhou, Jiangsu 215123, China.
Institute of Ageing & Chronic Disease, University of Liverpool, L7 8TX Liverpool, UK.
Nucleic Acids Res. 2021 Jan 8;49(D1):D1396-D1404. doi: 10.1093/nar/gkaa790.
Deciphering the biological impacts of millions of single nucleotide variants remains a major challenge. Recent studies suggest that RNA modifications play versatile roles in essential biological mechanisms, and are closely related to the progression of various diseases including multiple cancers. To comprehensively unveil the association between disease-associated variants and their epitranscriptome disturbance, we built RMDisease, a database of genetic variants that can affect RNA modifications. By integrating the prediction results of 18 different RNA modification prediction tools and also 303,426 experimentally-validated RNA modification sites, RMDisease identified a total of 202,307 human SNPs that may affect (add or remove) sites of eight types of RNA modifications (m6A, m5C, m1A, m5U, Ψ, m6Am, m7G and Nm). These include 4,289 disease-associated variants that may imply disease pathogenesis functioning at the epitranscriptome layer. These SNPs were further annotated with essential information such as post-transcriptional regulations (sites for miRNA binding, interaction with RNA-binding proteins and alternative splicing) revealing putative regulatory circuits. A convenient graphical user interface was constructed to support the query, exploration and download of the relevant information. RMDisease should make a useful resource for studying the epitranscriptome impact of genetic variants via multiple RNA modifications with emphasis on their potential disease relevance. RMDisease is freely accessible at: www.xjtlu.edu.cn/biologicalsciences/rmd.
解析数百万个单核苷酸变异的生物学影响仍然是一个主要挑战。最近的研究表明，RNA 修饰在重要的生物学机制中发挥着多种作用，并且与包括多种癌症在内的各种疾病的进展密切相关。为了全面揭示疾病相关变异与其表转录组干扰之间的关联，我们构建了 RMDisease，这是一个可以影响 RNA 修饰的遗传变异数据库。通过整合 18 种不同的 RNA 修饰预测工具的预测结果，以及 303426 个经过实验验证的 RNA 修饰位点，RMDisease 总共确定了 202307 个人类 SNP，这些 SNP 可能影响（添加或去除）八种类型的 RNA 修饰（m6A、m5C、m1A、m5U、Ψ、m6Am、m7G 和 Nm）的位点。其中包括 4289 个疾病相关变异，这些变异可能暗示疾病发病机制在表转录组层面发挥作用。这些 SNP 进一步注释了重要信息，如 miRNA 结合、与 RNA 结合蛋白相互作用和选择性剪接的转录后调控（结合位点），揭示了潜在的调控回路。构建了一个方便的图形用户界面，以支持相关信息的查询、探索和下载。RMDisease 将成为通过多种 RNA 修饰研究遗传变异的表转录组影响的有用资源，重点关注其潜在的疾病相关性。RMDisease 可免费访问：www.xjtlu.edu.cn/biologicalsciences/rmd。
