TY - JOUR
T1 - Deregulation of RNA polymerase III transcription in cervical epithelium in response to high-risk human papillomavirus
AU - Daly, Nicole L.
AU - Arvanitis, Demetrios A.
AU - Fairley, Jennifer A.
AU - Gomez-Roman, Natividad
AU - Morton, Jennifer P.
AU - Graham, Sheila V.
AU - Spandidos, Demetrios A.
AU - White, Robert J.
PY - 2005/1/27
Y1 - 2005/1/27
N2 - RNA polymerase (pol) III transcription is a major determinant of biosynthetic capacity, providing essential products such as tRNA and 5S rRNA. It is controlled directly by the tumour suppressors RB and p53. High-risk types of human papillomavirus (HPV), such as HPV16, express the oncoproteins E6 and E7 that can inactivate p53 and RB, respectively. Accordingly, both E6 and E7 stimulate pol III transcription in cultured cells. HPV16-positive cervical biopsies express elevated levels of tRNA and 5S rRNA when compared to biopsies that test negative for HPV or are infected with the lower risk HPV11. Integration of viral DNA into the host cell genome stimulates expression of E6 and E7 and correlates with induction of tRNA and 5S rRNA. Expression of mRNA encoding the pol III-specific transcription factor Brf1 also correlates with the presence of integrated HPV16. Brf1 levels are limiting for tRNA and 5S rRNA synthesis in cervical cells. Furthermore, pol III-transcribed genes that do not use Brf1 are not induced in HPV16-positive biopsies. Three complementary mechanisms may therefore allow high-risk HPV to stimulate production of tRNA and 5S rRNA: E6-mediated removal of p53; E7-mediated neutralization of RB; and induction of Brf1. The resultant increase in biosynthetic capacity may contribute to deregulated cell growth.
AB - RNA polymerase (pol) III transcription is a major determinant of biosynthetic capacity, providing essential products such as tRNA and 5S rRNA. It is controlled directly by the tumour suppressors RB and p53. High-risk types of human papillomavirus (HPV), such as HPV16, express the oncoproteins E6 and E7 that can inactivate p53 and RB, respectively. Accordingly, both E6 and E7 stimulate pol III transcription in cultured cells. HPV16-positive cervical biopsies express elevated levels of tRNA and 5S rRNA when compared to biopsies that test negative for HPV or are infected with the lower risk HPV11. Integration of viral DNA into the host cell genome stimulates expression of E6 and E7 and correlates with induction of tRNA and 5S rRNA. Expression of mRNA encoding the pol III-specific transcription factor Brf1 also correlates with the presence of integrated HPV16. Brf1 levels are limiting for tRNA and 5S rRNA synthesis in cervical cells. Furthermore, pol III-transcribed genes that do not use Brf1 are not induced in HPV16-positive biopsies. Three complementary mechanisms may therefore allow high-risk HPV to stimulate production of tRNA and 5S rRNA: E6-mediated removal of p53; E7-mediated neutralization of RB; and induction of Brf1. The resultant increase in biosynthetic capacity may contribute to deregulated cell growth.
KW - cervical cancer
KW - human papillomavirus (HPV)
KW - RNA polymerase III (pol III)
KW - TFIIIB
KW - transcription
UR - http://www.scopus.com/inward/record.url?scp=13444287805&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1208031
DO - 10.1038/sj.onc.1208031
M3 - Article
C2 - 15592529
AN - SCOPUS:13444287805
SN - 0950-9232
VL - 24
SP - 880
EP - 888
JO - Oncogene
JF - Oncogene
IS - 5
ER -