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Updated: Jan 15, 2026
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Productive mRNA chromatin escape is promoted by PRMT5 activity
Joseph D DeAngelo1, Maxim I Maron1, Jacob S Roth1
1Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.
Abstract:
Protein arginine methyltransferase 5 (PRMT5) catalyzes symmetric arginine dimethylation (Rme2s) of RNA-binding proteins and influences RNA splicing and gene expression. However, how PRMT5 couples splicing to productive transcript output remains unclear. We show that a major function of PRMT5 is to promote chromatin escape of mRNAs, designated as genomically retained incompletely processed polyadenylated transcripts (GRIPPs). Using nascent and spike-in normalized fractionated transcriptomics with proteomics, we find that PRMT5 inhibition in mammalian cells causes polyadenylated mRNA and Smith antigen (Sm) protein accumulation on chromatin. These retained transcripts are intron rich and splice slowly. PRMT5 inhibition and isogenic SNRPB mutants demonstrate that Sm tail methylation is essential to prevent RNA detention on chromatin. Biochemical assays reveal that the SMN Tudor domain competes with nucleic acid binding of methylated Sm tails. We conclude that PRMT5 ensures mRNA processing and nuclear export by preventing aberrant chromatin retention, highlighting arginine methylation as a key regulator of RNA-chromatin dynamics.
Insights
Protein arginine methyltransferase 5 (PRMT5) prevents mRNA retention on chromatin. This ensures proper RNA processing and nuclear export, highlighting arginine methylation
Area of Science:
- Molecular Biology
- Epigenetics
- RNA Biology
Background:
- Protein arginine methyltransferase 5 (PRMT5) catalyzes symmetric arginine dimethylation (Rme2s), impacting RNA splicing and gene expression.
- The precise mechanism by which PRMT5 links RNA splicing to transcript output remains largely unknown.
Purpose of the Study:
- To elucidate the role of PRMT5 in mRNA processing and nuclear export.
- To investigate how PRMT5 regulates the fate of incompletely processed transcripts.
Main Methods:
- Utilized nascent and spike-in normalized fractionated transcriptomics combined with proteomics in mammalian cells.
- Employed PRMT5 inhibition and isogenic SNRPB mutants.
- Conducted biochemical assays to analyze protein-RNA interactions.
Main Results:
- PRMT5 inhibition leads to the accumulation of polyadenylated mRNA and Smith antigen (Sm) proteins on chromatin.
- These retained transcripts are intron-rich and exhibit slow splicing kinetics.
- Sm tail methylation, regulated by PRMT5, is crucial for preventing RNA detention on chromatin.
Conclusions:
- PRMT5 plays a critical role in promoting mRNA chromatin escape, preventing the accumulation of genomically retained incompletely processed polyadenylated transcripts (GRIPPs).
- Arginine methylation by PRMT5 is essential for efficient mRNA processing and nuclear export.
- This study highlights arginine methylation as a key regulator of RNA-chromatin dynamics.
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