Work

Identification of DHX33 as a Mediator of rRNA Synthesis and Cell Growth

Year: 2011

Type: article

Abstract: In this report, we employed a lentiviral RNA interference screen to discover nucleolar DEAD/DEAH-box helicases involved in RNA polymerase I (Pol I)-mediated transcriptional activity. Our screen identified DHX33 as an important modulator of 47S rRNA transcription. We show that DHX33 is a cell cycle-regulated nucleolar protein that associates with ribosomal DNA (rDNA) loci, where it interacts with the RNA Pol I transcription factor upstream binding factor (UBF). DHX33 knockdown decreased the association of Pol I with rDNA and caused a dramatic decrease in levels of rRNA synthesis. Wild-type DHX33 overexpression, but not a DNA binding-defective mutant, enhanced 47S rRNA synthesis by promoting the association of RNA polymerase I with rDNA loci. In addition, an NTPase-defective DHX33 mutant (K94R) acted as a dominant negative mutant, inhibiting endogenous rRNA synthesis. Moreover, DHX33 deficiency in primary human fibroblasts triggered a nucleolar p53 stress response, resulting in an attenuation of proliferation. Thus, we show the mechanistic importance of DHX33 in rRNA transcription and proliferation.

Source: Molecular and Cellular Biology

DOI: 10.1128/mcb.05832-11

Authors: Yandong Zhang, Jason T. Forys, Alexander P. Miceli, Abigail S. Gwinn, Jason D. Weber

Institution: Washington University in St. Louis

Language: English

Topic: Nuclear Structure and Function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: U.S. Department of Defense, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences