5-Azacytidine incorporation into mRNAs disrupts translation and induces ribosome collisions.

5-Azacytidine treatment of cells causes time-dependent C-to-G conversion in mRNAs, enriched at A-site footprints, with ribosome collisions linked to translation inhibition.

• Why it matters: 5-Azacytidine is used for myeloid malignancies, but most of the drug is incorporated into RNA; how that alters translation and stress signaling is unclear.
• What they did: Cells were treated with 5-Azacytidine and analyzed by Ribo-seq, Disome-seq, and RNA-seq to map C-to-G conversion timing and its enrichment at A-site monosome and disome positions.
• The result: 5-Azacytidine activates ZAK- and GCN2-dependent stress responses, and ZNF598 loss sensitizes cells, implying ribosome collisions and translation disruption add to its mechanism.

AI summary of the abstract · may contain errors · not medical advice · read the paper.