Two isoforms of human RNA polymerase III with specific functions in cell growth and transformation.
Transcription in eukaryotic nuclei is carried out by DNA-dependent RNA polymerases I, II, and III. Human RNA polymerase III (Pol III) transcribes small untranslated RNAs that include tRNAs, 5S RNA, U6 RNA, and some microRNAs. Increased Pol III transcription has been reported to accompany or cause cell transformation. Here we describe a Pol III subunit (RPC32beta) that led to the demonstration of two human Pol III isoforms (Pol IIIalpha and Pol IIIbeta). RPC32beta-containing Pol IIIbeta is ubiquitously expressed and essential for growth of human cells. RPC32alpha-containing Pol IIIalpha is dispensable for cell survival, with expression being restricted to undifferentiated ES cells and to tumor cells. In this regard, and most importantly, suppression of RPC32alpha expression impedes anchorage-independent growth of HeLa cells, whereas ectopic expression of RPC32alpha in IMR90 fibroblasts enhances cell transformation and dramatically changes the expression of several tumor-related mRNAs and that of a subset of Pol III RNAs. These results identify a human Pol III isoform and isoform-specific functions in the regulation of cell growth and transformation.
Haurie
Valérie
V
Institut Européen de Chimie et Biologie/ Université de Bordeaux, Institut National de la Santé et de la Recherche Médicale U869, 33607 Pessac, France.
Durrieu-Gaillard
Stéphanie
S
Dumay-Odelot
Hélène
H
Da Silva
Daniel
D
Rey
Christophe
C
Prochazkova
Martina
M
Roeder
Robert G
RG
Besser
Daniel
D
Teichmann
Martin
M
D002454:Cell Differentiation; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D004591:Electrophoresis, Polyacrylamide Gel; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008969:Molecular Sequence Data; D012320:RNA Polymerase III / Q000378:metabolism*; D034741:RNA, Small Interfering
D007527:Isoenzymes; D034741:RNA, Small Interfering; D012320:RNA Polymerase III