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.