Rrn3 phosphorylation is a regulatory checkpoint for ribosome biogenesis

被引:57
作者
Cavanaugh, AH
Hirschler-Laszkiewicz, I
Hu, QY
Dundr, M
Smink, T
Misteli, T
Rothblum, LI
机构
[1] Sigfried & Janet Weis Ctr Res, Geisinger Clin, Danville, PA 17821 USA
[2] NCI, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1074/jbc.M201232200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cycloheximide inhibits ribosomal DNA (rDNA) transcription in vivo. The mouse homologue of yeast Rrn3, a polymerase-associated transcription initiation factor, can complement extracts from cycloheximide-treated mammalian cells. Cycloheximide inhibits the phosphorylation of Rrn3 and causes its dissociation from RNA polymerase I. Rrn3 interacts with the rpa43 subunit of RNA polymerase 1, and treatment with cycloheximide inhibits the formation of a Rrn3.rpa43, complex in vivo. Rrn3 produced in Sf9 cells but not in bacteria interacts with rpa43 in vitro, and such interaction is dependent upon the phosphorylation state of Rrn3. Significantly, neither dephosphorylated Rrn3 nor Rrn3 produced in Escherichia coli can restore transcription by extracts from cycloheximide-treated cells. These results suggest that the phosphorylation. state of Rrn3 regulates rDNA transcription by determining the steady-state concentration of the Rrn3.RNA polymerase I complex within the nucleolus.
引用
收藏
页码:27423 / 27432
页数:10
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