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Updated: Aug 28, 2025
08:35
Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
Published on: June 24, 2021
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Glucocorticoids mediate transcriptome-wide alternative polyadenylation: Potential mechanistic and clinical
Thanh Thanh L Nguyen1,2,3, Duan Liu1, Huanyao Gao1
1Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.
Clinical and Translational Science
|September 21, 2022
Summary
Glucocorticoids alter alternative polyadenylation (APA) in human cells, impacting gene function differently than gene expression. This finding reveals a new layer of genetic regulation with potential implications for immune disorders and drug therapies.
Area of Science:
- Genomics
- Molecular Biology
- Pharmacology
Background:
- Alternative polyadenylation (APA) is a key RNA processing event influencing gene function.
- Hormonal regulation of APA is poorly understood.
- Glucocorticoids are widely used drugs with diverse biological effects.
Purpose of the Study:
- To investigate the impact of glucocorticoids on transcriptome-wide APA in human B-lymphoblastoid cell lines.
- To explore the relationship between glucocorticoid-mediated APA and gene expression.
- To identify potential functional consequences and pharmacogenomic implications of glucocorticoid-regulated APA.
Main Methods:
- Transcriptome-wide analysis of APA.
- Gene expression profiling.
- Bioinformatic analysis of RNA-binding protein targets and pathway enrichment.
- Investigation of genotype-dependent APA.
Main Results:
- Glucocorticoids regulate APA for a subset of genes, potentially via altered expression of RNA-binding proteins.
- Genes with glucocorticoid-mediated APA are enriched in viral translation pathways, distinct from interferon/interleukin pathways for gene expression.
- Glucocorticoid-induced APA of LY6E was observed without changes in expression, relevant to COVID-19.
- Cell-type-specific and genotype-dependent (pharmacogenomic-alterative polyadenylation quantitative trait loci) glucocorticoid-mediated APA was identified.
Conclusions:
- Glucocorticoids significantly impact APA, offering a regulatory mechanism distinct from gene expression.
- Glucocorticoid-mediated APA may play a role in immune regulation and antiviral responses.
- Pharmacogenomic-alterative polyadenylation quantitative trait loci provide mechanisms for genetic variants in immune disorders.
- Understanding glucocorticoid-mediated APA could inform disease pathophysiology and drug therapy strategies.
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