ArticleScience advances2025
LEDGF/p75 promotes transcriptional pausing through preventing SPT5 phosphorylation.
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 6 papers.
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Who cites it
6 citing papers in PubMed.
- NS1-Induced PARP1 Phase Transitions Prolongs Host Transcriptional Pausing to Promote Influenza A Virus Replication.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multisite Threonine Phosphorylation in the SPT5 C-Terminal Region 1 Enables Sequence-Dependent Regulation without Global Structural Remodeling.The journal of physical chemistry. B · 2026Article
- Structure and function of IWS1 in transcription elongation.Nucleic acids research · 2026Article
- Relationship between the distribution of LEDGF along genes and positions of HIV-1 DNA integration.mBio · 2026Article
- The SP1-SuperEnhancer-SPHK1 Axis Mediates Niraparib Resistance in TNBC.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Tripartite phosphorylation of SPT5 by CDK9 times pause release and tunes elongation rate of RNA polymerase II.Molecular cell · 2025Article
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Authors and funding
12 authors.
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Abstract
SPT5 exhibits versatile functions in RNA Pol II promoter proximal pausing, pause release, and elongation in metazoans. However, the mechanism underlying the functional switch of SPT5 during early elongation has not been fully understood. Here, we report that the phosphorylation site-rich domain (PRD)/CTR1 and the prion-like domain (PLD)/CTR2, which are situated adjacent to each other within the C-terminal repeat (CTR) in SPT5, play pivotal roles in Pol II pausing and elongation, respectively. Our study demonstrates that LEDGF/p75 is highly enriched at promoters, especially paused promoters, and prevents the phosphorylation of SPT5 PRD by the super elongation complex (SEC). Furthermore, deletion of LEDGF IBD leads to increased SEC occupancies and SPT5 PRD phosphorylation at promoters and also increased pause release. In sum, our study reveals that LEDGF and SEC function cooperatively on SPT5 distinct domains to ensure proper transcriptional transition from pausing to elongation.
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