PUS7 mRNA pseudouridylation is driven by RNA sequence, structure, and cell-type-specific features.

PUS7's mRNA pseudouridylation is driven by specific RNA sequence, structure, and cell-type features, with USUAG being a key recognition motif.

• Why it matters: Understanding PUS7's specificity is crucial because it influences gene expression and is linked to neurodevelopmental disorders and cancer, yet its regulatory mechanisms remain unclear.
• What they did: Using Nano-Mod-Amp, a high-throughput Nanopore method, the study examined how RNA sequence, accessibility, and structure affect PUS7 activity across cell types, including perturbations through mutations and antisense oligos.
• The result: Findings show PUS7 activity depends on USUAG sequence, RNA structure, and cell-specific factors, enabling site-specific modulation of pseudouridines and offering insights into its regulatory mechanisms.