ArticleGenes & development2007
The Spt6 SH2 domain binds Ser2-P RNAPII to direct Iws1-dependent mRNA splicing and export.
Article in Genes & development, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers.
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157 citing papers in PubMed, 262 citations in OpenAlex.
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- Nuclear activities and interactome of the NS5 protein of Tick-Borne Encephalitis Virus.bioRxiv : the preprint server for biology · 2026Article
- Defective RNA processing and ELOA-mediated transcriptional elongation in reversible cellular senescence suggest aging by transcription.Molecular cell · 2025Article
- Dual Modes of Gene Regulation by CDK12.bioRxiv : the preprint server for biology · 2025Article
- IWS1 positions downstream DNA to globally stimulate Pol II elongation.Nature communications · 2025Article
- Molecular docking and biological evaluation of a novel IWS1 inhibitor for the treatment of human retroperitoneal liposarcoma.Scientific reports · 2025Article
- TDP-43 toxic gain of function links ALS, FTD and Alzheimer's Disease through splicing dysregulation.bioRxiv : the preprint server for biology · 2025Article
- Histone chaperones coupled to DNA replication and transcription control divergent chromatin elements to maintain cell fate.Genes & development · 2025Article
- Overlapping and distinct functions of SPT6, PNUTS, and PCF11 in regulating transcription termination.Nucleic acids research · 2025Article
- Genes and proteins expressed at different life cycle stages in the model protist Euplotes vannus revealed by both transcriptomic and proteomic approaches.Science China. Life sciences · 2025Article
- Nuclear mRNA export.Acta biochimica et biophysica Sinica · 2024Review
- The cell biology of HIV-1 latency and rebound.Retrovirology · 2024Review
- Mechanisms and Functions of the RNA Polymerase II General Transcription Machinery during the Transcription Cycle.Biomolecules · 2024Review
- A Revision of Herpes Simplex Virus Type 1 Transcription: First, Repress; Then, Express.Microorganisms · 2024Review
- Transcriptional elongation control in developmental gene expression, aging, and disease.Molecular cell · 2023Review
- Incomplete activation ofLife science alliance · 2023Article
- Insights into Spt6: a histone chaperone that functions in transcription, DNA replication, and genome stability.Trends in genetics : TIG · 2023Review
- Article
97 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Spt6 promotes transcription elongation at many genes and functions as a histone H3 chaperone to alter chromatin structure during transcription. We show here that mammalian Spt6 binds Ser2-phosphorylated (Ser2P) RNA polymerase II (RNAPII) through a primitive SH2 domain, which recognizes phosphoserine rather than phosphotyrosine residues. Surprisingly, a point mutation in the Spt6 SH2 domain (R1358K) blocked binding to RNAPIIo without affecting transcription elongation rates in vitro. However, HIV-1 and c-myc RNAs formed in cells expressing the mutant Spt6 protein were longer than normal and contained splicing defects. Ectopic expression of the wild-type, but not mutant, Spt6 SH2 domain, caused bulk poly(A)+ RNAs to be retained in the nucleus, further suggesting a widespread role for Spt6 in mRNA processing or assembly of export-competent mRNP particles. We cloned the human Spt6-interacting protein, hIws1 (interacts with Spt6), and found that it associates with the nuclear RNA export factor, REF1/Aly. Depletion of endogenous hIws1 resulted in mRNA processing defects, lower levels of REF1/Aly at the c-myc gene, and nuclear retention of bulk HeLa poly(A)+ RNAs in vivo. Thus binding of Spt6 to Ser2-P RNAPII provides a cotranscriptional mechanism to recruit Iws1, REF1/Aly, and associated mRNA processing, surveillance, and export factors to responsive genes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.