Fig. 3. Future directions for research into gene regulation by RNA modifications.

There are several unresolved questions in the field: Mechanistically, how do external stimuli regulate RNA modification to affect protein translation rates and transcription? How do RNA modifying enzymes act as metabolic sensors? How do RNA modifications directly or indirectly regulate chromatin regulatory complexes to affect chromatin state or transcription? What factors—such as transcription factors, chromatin, RNA, RBPs, or components of the RNA polymerase II complex— recruit m⁶A writer and eraser enzymes to their targets? What factors regulate and determine the target specificity of readers? How are the protein synthesis and transcription machineries coordinated by RNA modifications?