ArticleCell cycle (Georgetown, Tex.)2018
Regulation of RNA polymerase III transcription during transformation of human IMR90 fibroblasts with defined genetic elements.
Article in Cell cycle (Georgetown, Tex.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 43 citations in OpenAlex.
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- Structural insights into human TFIIIC promoter recognition.Science advances · 2023Article
- The POLR3G Subunit of Human RNA Polymerase III Regulates Tumorigenesis and Metastasis in Triple-Negative Breast Cancer.Cancers · 2022Article
- Pan-cancer characterization of metabolism-related biomarkers identifies potential therapeutic targets.Journal of translational medicine · 2021Article
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- Cryo-EM structures of human RNA polymerase III in its unbound and transcribing states.Nature structural & molecular biology · 2021Article
- RNA Polymerase III Subunit Mutations in Genetic Diseases.Frontiers in molecular biosciences · 2021Review
- Cell-cell fusion of mesenchymal cells with distinct differentiations triggers genomic and transcriptomic remodelling toward tumour aggressiveness.Scientific reports · 2020Article
- Dysregulation of Transcription Factor Activity During Formation of Cancer-Associated Fibroblasts.International journal of molecular sciences · 2020Article
- RNA polymerase III transcription as a disease factor.Genes & development · 2020Review
- Genome remodeling upon mesenchymal tumor cell fusion contributes to tumor progression and metastatic spread.Oncogene · 2020Article
- Article
- The hRPC62 subunit of human RNA polymerase III displays helicase activity.Nucleic acids research · 2019Article
- Fusion-mediated chromosomal instability promotes aneuploidy patterns that resemble human tumors.Oncogene · 2019Article
- Article
- Effects on prostate cancer cells of targeting RNA polymerase III.Nucleic acids research · 2019Article
- Differential regulation of RNA polymerase III genes during liver regeneration.Nucleic acids research · 2019Article
- The third (III) road to cell transformation.Cell cycle (Georgetown, Tex.) · 2018Article
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20 authors at 4 institutions in 2 countries.
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Abstract
RNA polymerase (Pol) III transcribes small untranslated RNAs that are essential for cellular homeostasis and growth. Its activity is regulated by inactivation of tumor suppressor proteins and overexpression of the oncogene c-MYC, but the concerted action of these tumor-promoting factors on Pol III transcription has not yet been assessed. In order to comprehensively analyse the regulation of Pol III transcription during tumorigenesis we employ a model system that relies on the expression of five genetic elements to achieve cellular transformation. Expression of these elements in six distinct transformation intermediate cell lines leads to the inactivation of TP53, RB1, and protein phosphatase 2A, as well as the activation of RAS and the protection of telomeres by TERT, thereby conducting to full tumoral transformation of IMR90 fibroblasts. Transformation is accompanied by moderately enhanced levels of a subset of Pol III-transcribed RNAs (7SK; MRP; H1). In addition, mRNA and/or protein levels of several Pol III subunits and transcription factors are upregulated, including increased protein levels of TFIIIB and TFIIIC subunits, of SNAPC1 and of Pol III subunits. Strikingly, the expression of POLR3G and of SNAPC1 is strongly enhanced during transformation in this cellular transformation model. Collectively, our data indicate that increased expression of several components of the Pol III transcription system accompanied by a 2-fold increase in steady state levels of a subset of Pol III RNAs is sufficient for sustaining tumor formation.
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