ArticleNucleic acids research2018
Integrator subunit 4 is a 'Symplekin-like' scaffold that associates with INTS9/11 to form the Integrator cleavage module.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 95 citations in OpenAlex.
- Unprocessed U1 snRNAs as a biomarker of INTS11- and BRAT1-related neurodevelopmental disorders.Genome medicine · 2026Article
- Integrator subunit IntS11 orchestrates the temporal dynamics of neural lineage progression in Drosophila.Cell & bioscience · 2026Article
- Integrator 20th anniversary: a molecular machine indispensable in development and disease.Trends in molecular medicine · 2026Review
- Characterizing a Unique Retinal Phenotype in INTS11-Associated Neurodevelopmental Disorder.Investigative ophthalmology & visual science · 2026Article
- Female Aging Affects Coilin Pattern in Mouse Cumulus Cells.Journal of developmental biology · 2026Article
- Defining the roles of the Integrator, NEXT, and nuclear exosome complexes in Drosophila oogenesis.Cell reports · 2025Article
- DNA-directed termination of mammalian RNA polymerase II.Genes & development · 2024Article
- The Integrator complex: an emerging complex structure involved in the regulation of gene expression by targeting RNA polymerase II.Functional & integrative genomics · 2024Review
- Cytoplasmic binding partners of the Integrator endonuclease INTS11 and its paralog CPSF73 are required for their nuclear function.Molecular cell · 2024Article
- Neuronal differentiation requires BRAT1 complex to remove REST from chromatin.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A role for the C. elegans Argonaute protein CSR-1 in small nuclear RNA 3' processing.PLoS genetics · 2024Article
- Article
- Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer.Open medicine (Warsaw, Poland) · 2024Article
- IntS6 and the Integrator phosphatase module tune the efficiency of select premature transcription termination events.Molecular cell · 2023Article
- Coilin and Cajal bodies.Nucleus (Austin, Tex.) · 2023Review
- Transcriptional elongation control in developmental gene expression, aging, and disease.Molecular cell · 2023Review
- Molecular details of the CPSF73-CPSF100 C-terminal heterodimer and interaction with Symplekin.Open biology · 2023Article
- Decoding the prognostic significance of integrator complex subunit 9 (INTS9) in glioma: links to TP53 mutations, E2F signaling, and inflammatory microenvironments.Cancer cell international · 2023Article
- 3'-End Processing of Eukaryotic mRNA: Machinery, Regulation, and Impact on Gene Expression.Annual review of biochemistry · 2023Review
- Bi-allelic variants in INTS11 are associated with a complex neurological disorder.American journal of human genetics · 2023Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Integrator (INT) is a transcriptional regulatory complex associated with RNA polymerase II that is required for the 3'-end processing of both UsnRNAs and enhancer RNAs. Integrator subunits 9 (INTS9) and INTS11 constitute the catalytic core of INT and are paralogues of the cleavage and polyadenylation specificity factors CPSF100 and CPSF73. While CPSF73/100 are known to associate with a third protein called Symplekin, there is no paralog of Symplekin within INT raising the question of how INTS9/11 associate with the other INT subunits. Here, we have identified that INTS4 is a specific and conserved interaction partner of INTS9/11 that does not interact with either subunit individually. Although INTS4 has no significant homology with Symplekin, it possesses N-terminal HEAT repeats similar to Symplekin but also contains a β-sheet rich C-terminal region, both of which are important to bind INTS9/11. We assess three functions of INT including UsnRNA 3'-end processing, maintenance of Cajal body structural integrity, and formation of histone locus bodies to conclude that INTS4/9/11 are the most critical of the INT subunits for UsnRNA biogenesis. Altogether, these results indicate that INTS4/9/11 compose a heterotrimeric complex that likely represents the Integrator 'cleavage module' responsible for its endonucleolytic activity.
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