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Updated: Feb 18, 2026

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
Regulation of RNA polymerase III transcription during transformation of human IMR90 fibroblasts with defined genetic
Stéphanie Durrieu-Gaillard1,2, Hélène Dumay-Odelot1,2, Galina Boldina1,2,3
1a Université de Bordeaux , ARNA Laboratory , F-33076 Bordeaux , France.
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.
Insights
Tumorigenesis involves increased RNA polymerase III (Pol III) transcription. Upregulation of Pol III components and specific RNAs supports tumor formation, offering new insights into cancer development.
Area of Science:
- Molecular Biology
- Cancer Biology
- Gene Regulation
Background:
- RNA polymerase (Pol) III transcribes essential small untranslated RNAs.
- Pol III activity is modulated by tumor suppressor inactivation and oncogene overexpression.
- The combined effects of these factors on Pol III transcription during tumorigenesis are not fully understood.
Purpose of the Study:
- To comprehensively analyze the regulation of Pol III transcription during tumorigenesis.
- To investigate the role of Pol III system components in cellular transformation.
- To assess if Pol III upregulation is sufficient to sustain tumor formation.
Main Methods:
- Utilized a model system with five genetic elements for cellular transformation.
- Analyzed six distinct transformation intermediate cell lines derived from IMR90 fibroblasts.
- Measured RNA and protein levels of Pol III subunits and transcription factors.
Main Results:
- Cellular transformation involved TP53, RB1 inactivation, RAS activation, and TERT-mediated telomere protection.
- Transformation correlated with moderately enhanced levels of specific Pol III-transcribed RNAs (7SK, MRP, H1).
- Several Pol III subunits and transcription factors (TFIIIB, TFIIIC, SNAPC1, POLR3G) showed increased mRNA and/or protein levels, with SNAPC1 and POLR3G strongly upregulated.
Conclusions:
- Increased expression of Pol III transcription system components accompanies tumor formation.
- A 2-fold increase in specific Pol III RNAs is sufficient to sustain tumor development.
- These findings highlight the critical role of Pol III transcription in sustaining tumorigenesis.
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