ArticleBMC genomics2017
Lung function associated gene Integrator Complex subunit 12 regulates protein synthesis pathways.
Article in BMC genomics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Regulation of RNA transcript elongation in metazoans and its relevance to disease.Nature reviews. Molecular cell biology · 2026Review
- Integrator 20th anniversary: a molecular machine indispensable in development and disease.Trends in molecular medicine · 2026Review
- Generative prediction of causal gene sets responsible for complex traits.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Integrator complex subunit 12 knockout overcomes a transcriptional block to HIV latency reversal.eLife · 2025Article
- Exploring genetic loci linked to COVID-19 severity and immune response through multi-trait GWAS analyses.Frontiers in genetics · 2025Article
- The Integrator complex: an emerging complex structure involved in the regulation of gene expression by targeting RNA polymerase II.Functional & integrative genomics · 2024Review
- Remote regulation of rs80245547 and rs72673891 mediated by transcription factors C-Jun and CREB1 affectiScience · 2023Article
- Genomic regulation of transcription and RNA processing by the multitasking Integrator complex.Nature reviews. Molecular cell biology · 2023Review
- Coevolution combined with molecular dynamics simulations provides structural and mechanistic insights into the interactions between the integrator complex subunits.Computational and structural biotechnology journal · 2023Article
- Extended lifespan of bronchial epithelial cells maintains normal cellular phenotype and transcriptome integrity.ERJ open research · 2021Article
- Defining a role for lung function associated gene GSTCD in cell homeostasis.Respiratory research · 2019Article
- Biallelic sequence variants in INTS1 in patients with developmental delays, cataracts, and craniofacial anomalies.European journal of human genetics : EJHG · 2019Article
- Exposure to lipopolysaccharide (LPS) reduces contractile response of small airways from GSTCD-/- mice.PloS one · 2019Article
- Integrator subunit 4 is a 'Symplekin-like' scaffold that associates with INTS9/11 to form the Integrator cleavage module.Nucleic acids research · 2018Article
- Chloride intracellular channel 1 (CLIC1) contributes to modulation of cyclic AMP-activated whole-cell chloride currents in human bronchial epithelial cells.Physiological reports · 2018Article
- SporadicCancer cell international · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundGenetic studies of human lung function and Chronic Obstructive Pulmonary Disease have identified a highly significant and reproducible signal on 4q24. It remains unclear which of the two candidate genes within this locus may regulate lung function: GSTCD, a gene with unknown function, and/or INTS12, a member of the Integrator Complex which is currently thought to mediate 3'end processing of small nuclear RNAs.
resultsWe found that, in lung tissue, 4q24 polymorphisms associated with lung function correlate with INTS12 but not neighbouring GSTCD expression. In contrast to the previous reports in other species, we only observed a minor alteration of snRNA processing following INTS12 depletion. RNAseq analysis of knockdown cells instead revealed dysregulation of a core subset of genes relevant to airway biology and a robust downregulation of protein synthesis pathways. Consistent with this, protein translation was decreased in INTS12 knockdown cells. In addition, ChIPseq experiments demonstrated INTS12 binding throughout the genome, which was enriched in transcriptionally active regions. Finally, we defined the INTS12 regulome which includes genes belonging to the protein synthesis pathways.
conclusionINTS12 has functions beyond the canonical snRNA processing. We show that it regulates translation by regulating the expression of genes belonging to protein synthesis pathways. This study provides a detailed analysis of INTS12 activities on a genome-wide scale and contributes to the biology behind the genetic association for lung function at 4q24.
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