| First Author | Zhang Y | Year | 2011 |
| Journal | Mol Cell Biol | Volume | 31 |
| Issue | 23 | Pages | 4676-91 |
| PubMed ID | 21930779 | Mgi Jnum | J:178781 |
| Mgi Id | MGI:5300123 | Doi | 10.1128/MCB.05832-11 |
| Citation | Zhang Y, et al. (2011) Identification of DHX33 as a mediator of rRNA synthesis and cell growth. Mol Cell Biol 31(23):4676-91 |
| abstractText | 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. |
