Regulation of RNA polymerase III transcription during transformation of human IMR90 fibroblasts with defined genetic elements
Cell Cycle. 2018-01-22; 17(5): 605-615
DOI: 10.1080/15384101.2017.1405881
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1. Cell Cycle. 2018;17(5):605-615. doi: 10.1080/15384101.2017.1405881. Epub 2018
Jan 22.
Regulation of RNA polymerase III transcription during transformation of human
IMR90 fibroblasts with defined genetic elements.
Durrieu-Gaillard S(1)(2), Dumay-Odelot H(1)(2), Boldina G(1)(2)(3), Tourasse
NJ(1)(2), Allard D(3), André F(3), Macari F(4), Choquet A(4), Lagarde
P(5)(6)(7), Drutel G(8), Leste-Lasserre T(8), Petitet M(1), Lesluyes T(5)(6),
Lartigue-Faustin L(5)(6), Dupuy JW(9), Chibon F(5)(6), Roeder RG(10), Joubert
D(4), Vagner S(3)(11), Teichmann M(1)(2).
Author information:
(1)a Université de Bordeaux , ARNA Laboratory , F-33076 Bordeaux , France.
(2)b INSERM, U1212 – CNRS UMR 5320 , ARNA Laboratory , F-33000 Bordeaux ,
France.
(3)c Institut Gustave Roussy , INSERM U981 , F-94805 Villejuif , France.
(4)d Institut de Génomique Fonctionnelle , UMR 5203 CNRS , F-34000 Montpellier ,
France.
(5)e Department of Biopathology , Institut Bergonié , Molecular Pathology Unit ,
F-33000 Bordeaux , France.
(6)f Génétique et Biologie des Sarcomes- INSERM U916 , F- 33000 Bordeaux ,
France.
(7)g Université de Bordeaux , F-33076 Bordeaux , France.
(8)h NeuroCentre François Magendie , INSERM U862 , F-33077 Bordeaux , France.
(9)i Université de Bordeaux , Plateforme Protéome – Centre Génomique
Fonctionnelle Bordeaux , 33076 Bordeaux , France.
(10)j The Rockefeller University , 1230 York Avenue, New York , NY 10065 , USA.
(11)k Institut Curie , CNRS UMR 3348, F-91405 Orsay , France.
Comment in
Cell Cycle. 2018;17(4):410-411. doi: 10.1080/15384101.2017.1419903.
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.
DOI: 10.1080/15384101.2017.1405881
PMCID: PMC5969553
PMID: 29171785 [Indexed for MEDLINE]