PRMT5 activity sustains histone production to maintain genome integrity.

ABSTRACT: Histone proteins package DNA into nucleosomes, forming chromatin and thereby safeguarding genome integrity. Proper histone expression is essential for cell proliferation and chromatin organization, yet the upstream regulators of histone supply remain incompletely understood. PRMT5-a cell essential type II protein arginine methyltransferase frequently overexpressed in cancer-catalyzes symmetric dimethylation of arginine residues. Using time-resolved nascent transcriptional profiling, quantitative proteomics, and imaging, we show that PRMT5 activity is required to sustain histone transcription and histone protein synthesis during S phase. PRMT5 inhibition or knockdown leads to rapid histone mRNA depletion, loss of histone proteins, and accumulation of replication-associated nuclear abnormali

SUBMITTER: Roth JS 

PROVIDER: S-EPMC12265569 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature