ArticleThe Journal of biological chemistry2013
Functional analysis of the integrator subunit 12 identifies a microdomain that mediates activation of the Drosophila integrator complex.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Polyamine metabolic enzyme SAT1 remodels the neuronal transcriptome and rescues α-synuclein toxicity in Drosophila.Amino acids · 2026Article
- Integrator subunit INTS12 links ribotoxic stress to transcription-coupled nucleotide excision repair.Nature structural & molecular biology · 2026Article
- Integrator 20th anniversary: a molecular machine indispensable in development and disease.Trends in molecular medicine · 2026Review
- Polyamine metabolic enzyme SAT1 remodels the neuronal transcriptome and rescues α-synuclein toxicity in Drosophila.Research square · 2026Article
- Fortilin binds CTNNA3 and protects it against phosphorylation, ubiquitination, and proteasomal degradation to guard cells against apoptosis.Communications biology · 2025Article
- Cytoplasmic binding partners of the Integrator endonuclease INTS11 and its paralog CPSF73 are required for their nuclear function.Molecular cell · 2024Article
- IntS6 and the Integrator phosphatase module tune the efficiency of select premature transcription termination events.Molecular cell · 2023Article
- Integrator is a global promoter-proximal termination complex.Molecular cell · 2023Review
- INTS13 variants causing a recessive developmental ciliopathy disrupt assembly of the Integrator complex.Nature communications · 2022Article
- Emerging insights into the function and structure of the Integrator complex.Transcription · 2021Review
- The Integrator Complex in Transcription and Development.Trends in biochemical sciences · 2020Review
- Integrator Recruits Protein Phosphatase 2A to Prevent Pause Release and Facilitate Transcription Termination.Molecular cell · 2020Article
- The Integrator complex cleaves nascent mRNAs to attenuate transcription.Genes & development · 2019Article
- Biallelic sequence variants in INTS1 in patients with developmental delays, cataracts, and craniofacial anomalies.European journal of human genetics : EJHG · 2019Article
- Integrator is a key component of human telomerase RNA biogenesis.Scientific reports · 2019Article
- Integrator subunit 4 is a 'Symplekin-like' scaffold that associates with INTS9/11 to form the Integrator cleavage module.Nucleic acids research · 2018Article
- Poly(A)-ClickSeq: click-chemistry for next-generation 3΄-end sequencing without RNA enrichment or fragmentation.Nucleic acids research · 2017Article
- Lung function associated gene Integrator Complex subunit 12 regulates protein synthesis pathways.BMC genomics · 2017Article
- In vivo characterization of the Drosophila mRNA 3' end processing core cleavage complex.RNA (New York, N.Y.) · 2015Article
- Genome wide screening of RNAi factors of Sf21 cells reveal several novel pathway associated proteins.BMC genomics · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The Drosophila integrator complex consists of 14 subunits that associate with the C terminus of Rpb1 and catalyze the endonucleolytic cleavage of nascent snRNAs near their 3' ends. Although disruption of almost any integrator subunit causes snRNA misprocessing, very little is known about the role of the individual subunits or the network of structural and functional interactions that exist within the complex. Here we developed an RNAi rescue assay in Drosophila S2 cells to identify functional domains within integrator subunit 12 (IntS12) required for snRNA 3' end formation. Surprisingly, the defining feature of the Ints12 protein, a highly conserved and centrally located plant homeodomain finger domain, is not required for reporter snRNA 3' end cleavage. Rather, we find a small, 45-amino acid N-terminal microdomain to be both necessary and nearly sufficient for snRNA biogenesis in cells depleted of endogenous IntS12 protein. This IntS12 microdomain can function autonomously, restoring full integrator processing activity when introduced into a heterologous protein. Moreover, mutations within the microdomain not only disrupt IntS12 function but also abolish binding to other integrator subunits. Finally, the IntS12 microdomain is sufficient to interact and stabilize the putative scaffold integrator subunit, IntS1. Collectively, these results identify an unexpected interaction between the largest and smallest integrator subunits that is essential for the 3' end formation of Drosophila snRNA.
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Registered trials
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.