ArticleScience advances2025
SPT5 regulates RNA polymerase II stability via Cullin 3-ARMC5 recognition.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- Mechanisms of transcription termination across the coding and noncoding loci of the genome.Nature reviews. Molecular cell biology · 2026Review
- Regulation of RNA transcript elongation in metazoans and its relevance to disease.Nature reviews. Molecular cell biology · 2026Review
- Polymerase face-off: emerging concepts in transcription-replication coordination.EMBO reports · 2026Review
- ELOF1 is a core component of the promoter-proximal paused RNA polymerase II complex.bioRxiv : the preprint server for biology · 2026Article
- K63-linked ubiquitylation of S2P-RNAPII regulates transcription in a DNAPK inter-dependent manner in response to double-strand breaks.Nucleic acids research · 2026Article
- NELF prevents transcriptional readthrough into DNA replication zones in cancer cells.EMBO reports · 2026Article
- Cytoplasmic mRNA decay by the antiviral nuclease RNase L promotes transcriptional repression.Cell reports · 2026Article
- RNA polymerase II degradation triggered by DNA repair occurs in trans and independently of how the lesion is recognized.Nucleic acids research · 2026Article
- Defective RNA processing and ELOA-mediated transcriptional elongation in reversible cellular senescence suggest aging by transcription.Molecular cell · 2025Article
- Transcription quality control at the promoter-proximal checkpoint.Genes & development · 2025Review
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The stability of RNA polymerase II (Pol II) is tightly regulated during transcriptional elongation for proper control of gene expression. Our recent studies revealed that promoter-proximal Pol II is destabilized via the ubiquitin E3 ligase cullin 3 (CUL3) upon loss of transcription elongation factor SPT5. Here, we investigate how CUL3 recognizes chromatin-bound Pol II as a substrate. Using an unbiased proteomic screening approach, we identify armadillo repeat-containing 5 (ARMC5) as a CUL3 adaptor required for VCP/p97-dependent degradation of SPT5-depleted, chromatin-bound Pol II. Genome-wide analyses indicate that ARMC5 targets promoter-proximal Pol II in a BTB domain-dependent manner. Further biochemical analysis demonstrates that interaction between ARMC5 and Pol II requires the transcriptional cyclin-dependent kinase 9 (CDK9), supporting a phospho-dependent degradation model. We propose that defective, promoter-proximal Pol II that lacks SPT5 is rapidly eliminated from chromatin in a noncanonical early termination pathway that requires CDK9-dependent interaction with the CUL3-ARMC5 ubiquitin ligase complex.
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