Cell genomicsJul 30, 2026

PUS7 changes RNA by modifying specific letters based on RNA sequence, shape, and cell type

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 3, 2026

Abstract

PUS7 influences gene expression and is linked to neurodevelopmental disorders and cancer.

PUS7 recognizes a common RNA sequence known as UNUAR.
Key factors driving mRNA modification by PUS7 include the USUAG sequence, the accessibility of the target uridine, and the RNA structure.
Mutations or antisense oligos that alter RNA structure can change pseudouridine levels.
Pseudouridine levels in cells respond to changes in PUS7 levels, indicating its regulatory potential.
PUS7 activity varies across different cell types, which may involve RNA-binding proteins or other cellular factors.

Simplified

PUS7 is a major mRNA pseudouridine synthase that influences gene expression and is dysregulated in neurodevelopmental disorders and cancer. PUS7 recognizes a prevalent and degenerate UNUAR sequence, but the mechanisms underlying PUS7's specificity remain unknown. We developed Nano-Mod-Amp, a targeted Nanopore high-throughput pseudouridine detection method, to interrogate PUS7 regulatory features. We established that USUAG, accessibility of the target uridine, and RNA structure are drivers of mRNA modification by PUS7. Perturbing structure through mutations or antisense oligos modulates pseudouridine levels. In cells, pseudouridines are responsive to PUS7 levels, demonstrating the regulatory potential of varying PUS7 levels across cell states. Conversely, PUS7 activity varies across cell types independently of expression levels, suggesting a potential regulatory role for RNA-binding proteins, RNA structure, or other cellular factors. We uncovered principles guiding PUS7 activity, enabling site-specific modulation of pseudouridines. These epitranscriptomic mechanisms provide molecular insight into the regulation and dysregulation of PUS7.

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PubMed

PUS7 changes RNA by modifying specific letters based on RNA sequence, shape, and cell type

Abstract

Full Text

Funding

Competing interests

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