# Molecular Insights into Widespread Pseudouridine RNA Modifications: Implications for Women’s Health and Disease

## TL;DR

Pseudouridine RNA modifications are linked to women's health and diseases like cancer, offering potential as biomarkers and therapeutic targets.

## Contribution

The paper highlights pseudouridine's role in women's cancers and non-cancer conditions, emphasizing its potential as a biomarker and therapeutic target.

## Key findings

- Abnormal pseudouridine levels and modifying enzymes are linked to breast, ovarian, endometrial, and cervical cancers.
- Pseudouridine synthases like PUS1 and dyskerin alter RNA modification patterns, influencing cancer progression.
- Pseudouridine dysregulation correlates with tumor burden, metastasis, and treatment response in women's cancers.

## Abstract

Pseudouridine (Ψ) is the most common chemical modification found in RNA and helps RNA molecules fold correctly, remain stable, and function properly in cells. Ψ levels also change in many normal and disease conditions, such as during immune responses, metabolic disorders, stress, and pregnancy complications like preeclampsia. Recent research shows that abnormal regulation of Ψ and the enzymes that produce it can contribute to several cancers affecting women, including breast, ovarian, endometrial, and cervical cancers. Higher Ψ levels in blood, urine, or tumor tissue often reflect larger tumors, metastasis, or how patients respond to treatment. Enzymes such as PUS1, PUS7, and dyskerin can alter RNA modification patterns and influence cancer growth. Because of this, Ψ and its modifying enzymes may serve as useful biomarkers and potential therapeutic targets in women’s cancers, while also indicating changes in various non-cancer conditions.

Pseudouridine (Ψ), the most abundant RNA modification, plays essential roles in shaping RNA structure, stability, and translational output. Beyond cancer, Ψ is dynamically regulated across numerous physiological and pathological contexts—including immune activation, metabolic disorders, stress responses, and pregnancy-related conditions such as preeclampsia—where elevated Ψ levels reflect intensified RNA turnover and modification activity. These broad functional roles highlight pseudouridylation as a central regulator of cellular homeostasis. Emerging evidence demonstrates that Ψ dysregulation contributes directly to the development and progression of several women’s cancers, including breast, ovarian, endometrial, and cervical malignancies. Elevated Ψ levels in tissues, blood, and urine correlate with tumor burden, metastatic potential, and therapeutic responsiveness. Aberrant activity of Ψ synthases such as PUS1, PUS7, and the H/ACA ribonucleoprotein component dyskerin alters pseudouridylation patterns across multiple RNA substrates, including rRNA, tRNA, mRNA, lncRNAs, snoRNAs, and ncRNAs. These widespread modifications reshape ribosome function, modify transcript stability and translational efficiency, reprogram RNA–protein interactions, and activate oncogenic signaling programs. Advances in high-resolution, site-specific Ψ mapping technologies have further revealed mechanistic links between pseudouridylation and malignant transformation, highlighting how modification of distinct RNA classes contributes to altered cellular identity and tumor progression. Collectively, Ψ and its modifying enzymes represent promising biomarkers and therapeutic targets across women’s cancers, while also serving as sensitive indicators of diverse non-cancer physiological and disease states.