Molecular functions, cellular responses and pathological implications of the RNA modification N⁶-methyladenosine

The RNA modification N⁶-methyladenosine (m⁶A) precisely regulates eukaryotic gene expression. The deposition of m⁶A is governed by chromatin environment, transcription and RNA processing. m⁶A modifications influence chromatin function and RNA splicing, stability, localization and translation, and enable cellular adaptation to environmental changes. Dysregulation of m⁶A has been implicated in pathological processes, including neurodegenerative diseases and cancer. In this Review, we dissect the m⁶A machinery by describing how writers and erasers coordinate m⁶A deposition and reader proteins translate these modifications into diverse functional outcomes. We illustrate how this dynamic regulatory network orchestrates cellular stress responses, metabolic homeostasis and antitumour immunity, and outline the pathological consequences of m⁶A dysregulation in brain disorders and cancer. Finally, we highlight translational prospects of m⁶A biology, including the development of specific small-molecule inhibitors and precise editing technologies, and address the remaining challenges for clinical interventions targeting m⁶A.