RNA modification-mediated multidimensional crosstalk: a novel perspective on gene expression regulation

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.