Transcriptome-wide analysis for glucocorticoid receptor-mediated mRNA decay reveals various classes of target...

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• The glucocorticoid receptor (GR) regulates gene expression by binding to DNA or RNA.
• While GR's role in transcriptional regulation is known, its mechanism in rapid mRNA degradation is unclear.

Purpose of the Study:

• To elucidate the molecular mechanisms of glucocorticoid-induced GR-mediated mRNA decay (GMD).
• To identify the cellular locations and targets of GMD.

Main Methods:

• Cross-linking immunoprecipitation coupled with high-throughput sequencing (CLIP-seq) for GR, YBX1, and HRSP12.
• mRNA sequencing to identify endogenous GMD substrates.

Main Results:

• GMD occurs in both the nucleus and cytoplasm, affecting pre-mRNAs and mRNAs.
• Identified specific binding sites for GR, YBX1, and HRSP12 on targeted transcripts.
• Demonstrated that transcripts with these common binding sites are preferential GMD targets.

Conclusions:

• GR-mediated mRNA decay is a significant regulatory pathway.
• GMD targets a range of cellular transcripts, suggesting novel roles in biological events.
• The findings provide a foundation for understanding GMD's broader implications in cellular processes.