RMDisease: a database of genetic variants that affect RNA modifications, with implications for epitranscriptome pathogenesis

Abstract

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.

Prognostic Significance and Tumor Immune Microenvironment Heterogenicity of m5C RNA Methylation Regulators in Triple-Negative Breast Cancer

“…There have been several reports that gene mutations usually cause phenotypic changes, which are in turn closely related to carcinogenesis and aging (Gonzalo et al, 2017;Kaur et al, 2018;Chen et al, 2021). Concurrently, a meta-analysis of studies on copy number amplification has shown that copy number changes affect genes involved in cell cycle regulation, retinoic acid signaling, complement system, and antigen presentation, which may cause cancer (Brown et al, 2016).…”

“…Recent studies suggested that gene alterations may affect RNA modifications and disease associations (Song et al, 2020;Chen et al, 2021). Here, we analyzed the alterations in NSUN2 and NSUN6 from the cBioportal database, with these alterations mainly including mutations, deletions, copy number gains, and amplifications.…”

Recent advances in functional annotation and prediction of the epitranscriptome

“…Similar to m6AVar, m 6 A-Atlas also annotated the potential involvement of m 6 A sites in pathogenesis by integrating GWAS information. Similar to RMVar, RMDisease [131] collected eight types of RNA modifications and their disease-associated variants. Importantly, RMDisease integrated multiple algorithms and used more information and provides quantitatively the impact of the genetic variants on RNA modification.…”

Dynamics of m6A RNA Methylome on the Hallmarks of Hepatocellular Carcinoma

“…Furthermore, comprehensive information on reliable m6A methylation sites and peaks from MeRIP-seq data are summarized in m6A-Atlas ( Tang et al, 2020 ) and REPIC ( Liu et al, 2020b ), respectively. Bioinformatics resources such as RMDisease ( Chen K. et al, 2020 ) and RMVar ( Luo et al, 2020 ) can aid in better understanding the association between various epitranscriptomic modifications and their probable disease relevance.…”