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Human dyskerin binds to cytoplasmic H/ACA-box-containing transcripts affecting nuclear hormone receptor dependence
Federico Zacchini1,2, Giulia Venturi1,2, Veronica De Sanctis3
1Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale (DIMES), Alma Mater Studiorum - Università di Bologna, I-40138, Bologna, Italy.
Genome Biology
|August 22, 2022
Summary
Dyskerin depletion impacts mRNA processing, affecting nuclear hormone receptor pathways in breast cancer. This suggests a cytoplasmic role for dyskerin in regulating gene expression relevant to cancer progression.
Area of Science:
- Molecular Biology
- Cancer Research
- RNA Biology
Background:
- Dyskerin is a nuclear protein crucial for RNA modification.
- Defective dyskerin function is linked to human cancers and altered gene expression.
- This study investigates dyskerin's role in regulating mRNAs in breast cancer cells.
Purpose of the Study:
- To identify mRNAs regulated by dyskerin in human breast cancer cells.
- To understand the cytoplasmic function of dyskerin in post-transcriptional regulation.
- To explore the link between dyskerin, nuclear hormone receptors, and breast cancer.
Main Methods:
- Depletion of dyskerin in human breast cancer cells.
- Analysis of mRNA expression and polysome association.
- Characterization of the cytoplasmic dyskerin RNA interactome.
- In vivo xenograft experiments in nude mice.
Main Results:
- Dyskerin depletion affects mRNA isoforms with retained H/ACA box snoRNA-containing introns (snoRTs).
- Dyskerin binds to cytoplasmic snoRT fragments and protein-coding transcripts.
- Dyskerin dysregulation impacts nuclear hormone receptor ligand dependence in breast cancer cells.
- Reduced dyskerin promotes tumor growth in estrogen-dependent cells without estrogen.
Conclusions:
- Dyskerin has a cytoplasmic function influencing mRNA post-transcriptional networks.
- This cytoplasmic role is relevant to nuclear hormone receptor functions in cancer.
- Dyskerin may be a potential therapeutic target in hormone-dependent breast cancers.
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