RNA modifications play pivotal roles in regulating RNA metabolism. Notably, they do not function in isolation, but crosstalk with DNA/protein modifications and other RNA modifications to form multi-layered regulatory networks that cooperatively fine-tune gene expression. In this review, we propose a two-dimensional, mutually exclusive "cis/trans" and "direct/indirect" framework to delineate the mechanisms and functions of four reciprocal modification axes including RNA-DNA, RNA-histone, RNA-non-histone, and RNA-RNA interactions. Furthermore, this RNA modification-centered crosstalk provides groundbreaking insights into translational applications across disease therapy, tissue engineering, and plant biotechnology. We also address current technical challenges and outline future directions to accelerate translational research.
Wang et al. (Tue,) studied this question.