m6A is a well-known post-transcriptional modification that is dynamic and reversible, which is regulated by RNA modifiers that are placed under 2 groups: "writer" and "eraser". Writers, that is m6A methyltransferases, direct m6A modification by transfering the methyl group from S-adenosyl methionine to RNA nucleotides; and erasers, is the m6A demethylases, remove m6A from modified RNAs. What is noteworthy is that the roles of m6A on targeted RNAs depend on the functions of different RNA binding proteins that is 3th group of RNA modifiers, called readers. Inversely, some RBPs binding to RNA modification sites to perform their biological roles, like promoting the degradation of RNAs with modifications.
We intersected RBP binding sites with RNA modification sites stored in ENCOME to obtain regulatory pairs for six species, that are Human, Mouse, Yeast, Fly, C.elegans and A.thaliana. Then, we annotated the RBPs that were putatively affected by RNA modifications as reader for m6A and m6C, writer for m6A, m5C and Pseudo, and eraser for m6A. There are thousands of regulatory pairs about different RBPs, as follows:
|Reader (m6A; m5C; Pseudo)||633520; 22; 0||878; 0; 0||0; 0; 0||0; 0; 0||0; 0; 0||0; 0; 0|
|Writer (m6A; m5C; Pseudo)||25772; 29; 25||0; 0; 0||0; 0; 0||0; 0; 0||0; 0; 0||0; 0; 0|
|Eraser (m6A; m5C; Pseudo)||8517; 0; 0||0; 0; 0||0; 0; 0||0; 0; 0||0; 0; 0||0; 0; 0|
In RNAmod-RBP module, we collected and analyzed different RBP data of diverse RNA modification types among 6 species. As shown below:
miRNA are small endogenous RNAs that regulate gene-expression post-transcriptionally by binding target RNAs. While researches point that there are amounts of RNA modification sites located within miRNA binding sites.
For Human and Mouse, we classed miRNA targets into five groups, that are mRNAs, circRNAs, lncRNAs, pseudogenes and sncRNAs. Then we analyzed the distribution of all RNA modification sites stored in ENCOME on miRNA binding sites. The data were summarized as follows:
|mirRNA Target Type||Human||Mouse|
A significant number of genetic variants related to human diseases or phenotypes, and some RNA modifications have also been found to be correlated with these diseases and cancers, such as ALL and BRCA. Whether some RNA modifications may be the real causation for diseases and cancers.
We collected two classes of variant data of human, single-nucleotide variations (SNV) and single-nucleotide polymorphism (SNP) and analyzed them with RNA modifications. There are dozens of RNA modification types related to genetic variants, 14 for SNP and 27 fo SNV respectively. The overview as follows:
|Variant Type||Regulatory Pairs||Related RNA Modification Types|
|SNP||3904||A-I, Am, Cm, D, Gm, i6A, m1A, m2,2,7Gpp(pN), m5C, m6A, m7G, Um, xU, Y|
|SNV||971455||acp3U, A-I, Am, Cm, D, f5C, Gm, m1A, m1G, m1I, m2,2,7Gpp(pN), m2,2G, m2G, m3C, m5C, m5U, m5Um, m6A, m6Am, m7G, mpp(pN), QtRNA, t6A, Um, xG, xU, Y|