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.

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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