Abstract
The m6A modification has been implicated as an important epitranscriptomic marker, which plays extensive roles in the regulation of transcript stability, splicing, translation, and localization. Nevertheless, only some genes are repeatedly modified across various conditions and the principle of m6A regulation remains elusive. In this study, we performed a systems-level analysis of human genes frequently regulated by m6A modification (m6Afreq genes) and those occasionally regulated by m6A modification (m6Aocca genes). Compared to the m6Aocca genes, the m6Afreq genes exhibit gene importance-related features, such as lower dN/dS ratio, higher protein–protein interaction network degree, and reduced tissue expression specificity. Signaling network analysis indicates that the m6Afreq genes are associated with downstream components of signaling cascades, high-linked signaling adaptors, and specific network motifs like incoherent feed forward loops. Moreover, functional enrichment analysis indicates significant overlaps between the m6Afreq genes and genes involved in various layers of gene expression, such as being the microRNA targets and the regulators of RNA processing. Therefore, our findings suggest the potential interplay between m6A epitranscriptomic regulation and other gene expression regulatory machineries.
Highlights
Various types of RNA modifications can change the chemical or structural properties of the nucleotide residues and constitute the core mechanism of the epitranscriptomic regula-hsc.pku.edu.cn (Cui Q). a ORCID: 0000-0001-5685-066X. b ORCID: 0000-0003-3018-5221.Peer review under responsibility of Beijing Institute of Genomics, Chinese Academy of Sciences and Genetics Society of China.tion [1,2]
Considering not all genes are expressed under the 38 conditions covered in our dataset, we corrected the number of m6A modified conditions by dividing the number of tissue/cell types in which the gene is expressed
To probe the biological characteristics related to such distribution, we performed comprehensive analyses to compare the features of m6Afreq genes and m6Aocca genes
Summary
Corrected number of m6A regulated conditions m6Afreq genes show gene importance-related features The corrected number of m6A regulated conditions shows positive correlations with PPI network degree, but negative correlations with dN/dS ratio and the tissue expression specificity. No significant difference was observed in the network degree with respect to the directed edges when comparing the m6Afreq genes and m6Aocca genes (Wilcoxon’s test P = 0.611).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
