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Titolo:
Increased expression of UBF is a critical determinant for rRNA synthesis and hypertrophic growth of cardiac myocytes
Autore:
Brandenburger, Y; Jenkins, A; Autelitano, DJ; Hannan, RD;
Indirizzi:
Baker Med Res Inst, Mol Physiol Lab, Melbourne, Vic 8008, Australia Baker Med Res Inst Melbourne Vic Australia 8008 urne, Vic 8008, Australia
Titolo Testata:
FASEB JOURNAL
fascicolo: 9, volume: 15, anno: 2001,
pagine: NIL_146 - NIL_171
SICI:
0892-6638(200107)15:9<NIL_146:IEOUIA>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
RNA-POLYMERASE-I; TRANSCRIPTION FACTOR UBF; RIBOSOMAL DNA-TRANSCRIPTION; NF-KAPPA-B; UPSTREAM BINDING-FACTOR; RDNA TRANSCRIPTION; NEONATAL CARDIOMYOCYTES; PROTEIN-SYNTHESIS; HEART-CELLS; S6 KINASE;
Keywords:
rDNA transcription; cardiomyocyte hypertrophy; antisense RNA; adenovirus;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Hannan, RD Baker Med Res Inst, Mol Physiol Lab, POB 6492,St Kilda Rd Cent,Melbourne,Vic 8008, Australia Baker Med Res Inst POB 6492,St Kilda Rd CentMelbourne Vic Australia 8008
Citazione:
Y. Brandenburger et al., "Increased expression of UBF is a critical determinant for rRNA synthesis and hypertrophic growth of cardiac myocytes", FASEB J, 15(9), 2001, pp. NIL_146-NIL_171

Abstract

Recent evidence suggests that increased translational efficiency of existing ribosomes alone is insufficient to account for the hypertrophic growth of cardiomyocytes and that synthesis of new functional ribosomes must occur. The rate-limiting step in ribosome accumulation is the transcription of the ribosomal 45S genes (rDNA) by RNA polymerase I. Our previous studies havedemonstrated that increases in the expression of the rDNA transcription factor UBF correlated with hypertrophy of neonatal cardiomyocytes. These studies expand this observation to examine directly the hypothesis that increased UBF levels are an essential requirement for the initiation of cardiac hypertrophy. We demonstrate that the introduction of UBF antisense RNA into myocytes, using adenovirus approaches, efficiently inhibits UBF accumulationduring induction of cardiomyocyte hypertrophy. Moreover, this approach results in a significant reduction in rDNA transcription, rRNA levels, and protein accumulation, which are all the hallmarks of cardiac growth. Furthermore, UBF antisense RNA expression did not alter reexpression of the fetal gene program, which confirmed that the effect was specific for transcription by RNA polymerase I. These findings demonstrate that an increase in rRNA synthesis is required for hypertrophy of cardiomyocytes and also implicate UBF as a major regulatory factor in this process. Approaches that target UBF activity may be of therapeutic use in the regression of pathophysiological cardiac hypertrophy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 14:17:33