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O-GlcNAc regulates gene expression by controlling detained intron splicing
Zhi-Wei Tan1, George Fei1, Joao A Paulo2
1Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Nucleic Acids Research
|April 25, 2020
Summary
O-GlcNAc modification controls intron splicing to regulate gene expression. This mechanism links nutrient levels to cellular transcription, impacting global gene expression patterns.
Area of Science:
- Molecular Biology
- Gene Regulation
- Post-translational Modifications
Background:
- Intron detention regulates gene expression in eukaryotes, but its control mechanisms are unclear.
- O-GlcNAc, a nutrient-sensitive post-translational modification, integrates cellular signaling pathways.
Purpose of the Study:
- To investigate the role of O-GlcNAc in controlling detained intron splicing.
- To elucidate how O-GlcNAc modification impacts gene expression and cellular homeostasis.
Main Methods:
- Utilized specific inhibitors for O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
- Analyzed splicing of conserved detained introns in OGT and OGA genes.
- Assessed global changes in detained intron splicing under varying O-GlcNAc levels.
Main Results:
- O-GlcNAc directly regulates splicing of detained introns in OGT and OGA, buffering O-GlcNAc level fluctuations.
- OGT and OGA exhibit distinct mechanisms for gene expression control via detained intron splicing.
- Low O-GlcNAc levels enhance splicing of most detained introns, with minimal impact on other splicing pathways.
Conclusions:
- O-GlcNAc acts as a key regulator of detained intron splicing.
- Detained intron splicing controlled by O-GlcNAc tunes system-wide gene expression.
- This mechanism couples nutrient availability to the transcriptional program of the cell.
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