Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus
- Division of Molecular Biology of the Cell II, German Cancer Research Center, D-69120 Heidelberg, Germany
This extract was created in the absence of an abstract.
Mammalian cells contain 100 or more copies of tandemly repeated ribosomal RNA (rRNA) genes per haploid genome. These genes are transcribed with high efficiency to keep up with the cell's metabolic activity and demand for ribosomes. Alterations in cell proliferation are accompanied by profound changes in the transcription rate of rRNA genes. Thus, by responding to changes in the cellular environment, transcription by RNA polymerase I (Pol I) ultimately determines ribosome production and the potential for cell growth and proliferation. There are several comprehensive reviews that discuss regulation of rRNA synthesis in vertebrates and yeast (Grummt 1999; Reeder 1999; Warner 1999; Moss and Stefanovsky 2002). However, new data have been produced even since the latest of these reviews that uncover the mechanisms that link Pol I transcription to cellular physiology. In this review, I restrict the background information to the minimal level that is required for understanding initiation complex formation at the rDNA promoter before proceeding to review the regulatory pathways that adapt cellular rRNA synthesis to cell metabolism and growth.
Structural organization of the rRNA transcription unit
In higher vertebrates, a standard rDNA transcription unit encodes the precursor to 18S, 28S, and 5.8S rRNAs. Each unit also contains important sequence elements that regulate pre-rRNA transcription, such as the rDNA promoter, enhancers, spacer promoters, an origin of replication, transcription terminators, and a replication fork barrier that prevents replication forks from colliding with transcribing RNA polymerase I during S phase. The tandem arrangement of multiple rDNA genes may have been useful to increase gene dosage and to maintain the well-recognized rRNA sequence homology. With the exception of closely related species, eukaryotic rDNA promoter sequences have diverged significantly. Consistent with this sequence disparity, rDNA transcription is generally specific to taxonomic orders, the promoter of one group not being recognized by the transcription machinery of others (for …
