Tau is an m6A-associated RNA binding protein that causes RNA dysregulation in disease

Tau binds broadly to neuron-specific transcripts in MAPT V337M iPSC-derived neurons, with binding overlapping significantly with m6A peaks and resembling hnRNPA2B1’s 3'UTR profile.

• Why it matters: The molecular basis of tau pathogenicity in MAPT coding-variant dementia is unclear, despite widespread RNA-binding protein and RNA dysregulation signals in patient and iNeuron models.
• What they did: Postmortem brain and MAPT V337M iNeurons were profiled for RNA-binding protein abundance and RNA levels; a CRISPRi screen identified m6A-associated regulators, and eCLIP mapped tau–RNA binding.
• The result: hnRNPA2B1 knockdown or m6A-writer inhibition reduced tau binding to mRNAs, and hnRNPA2B1 hyperphosphorylation and RNA-binding redistribution in MAPT V337M iNeurons linked tau to RNA dysregulation relevant to hnRNPA2B1 function.