Emerging interactions between RNA methylation and chromatin architecture

Epitranscriptomics, the study of chemical modifications of RNA molecules, is increasingly recognized as an important component of gene expression regulation. While the majority of research has focused on N⁶-methyladenosine (m⁶A) RNA methylation on mRNAs, emerging evidence has revealed that the m⁶A modification extends beyond mRNAs to include chromatin-associated RNAs (caRNAs). CaRNAs constitute an important class of RNAs characterized by their interaction with the genome and epigenome. These features allow caRNAs to be actively involved in shaping genome organization. In this review, we bring into focus recent findings of the dynamic interactions between caRNAs and chromatin architecture and how RNA methylation impacts caRNAs’ function in this interplay. We highlight several enabling techniques, which were critical for genome-wide profiling of caRNAs and their modifications. Given the nascent stage of the field, we emphasize on the need to address critical gaps in study of these modifications in more relevant biological systems. Overall, these exciting progress have expanded the scope and reach of epitranscriptomics, unveiling new mechanisms that underpin the control of gene expression and cellular phenotypes, with potential therapeutic implications.