Basic mechanisms in RNA polymerase I transcription of the ribosomal RNA genes - PubMed (original) (raw)

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Basic mechanisms in RNA polymerase I transcription of the ribosomal RNA genes

Sarah J Goodfellow et al. Subcell Biochem. 2013.

Abstract

RNA Polymerase (Pol) I produces ribosomal (r)RNA, an essential component of the cellular protein synthetic machinery that drives cell growth, underlying many fundamental cellular processes. Extensive research into the mechanisms governing transcription by Pol I has revealed an intricate set of control mechanisms impinging upon rRNA production. Pol I-specific transcription factors guide Pol I to the rDNA promoter and contribute to multiple rounds of transcription initiation, promoter escape, elongation and termination. In addition, many accessory factors are now known to assist at each stage of this transcription cycle, some of which allow the integration of transcriptional activity with metabolic demands. The organisation and accessibility of rDNA chromatin also impinge upon Pol I output, and complex mechanisms ensure the appropriate maintenance of the epigenetic state of the nucleolar genome and its effective transcription by Pol I. The following review presents our current understanding of the components of the Pol I transcription machinery, their functions and regulation by associated factors, and the mechanisms operating to ensure the proper transcription of rDNA chromatin. The importance of such stringent control is demonstrated by the fact that deregulated Pol I transcription is a feature of cancer and other disorders characterised by abnormal translational capacity.

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Figures

Fig. 10.1

Fig. 10.1. Mammalian rDNA repeat and 47S rRNA promoter

The top panel illustrates key elements and the general organisation of a mammalian rDNA repeat. The IGS includes the spacer and 47S rRNA promoters, enhancer repeats and the TTF-I binding sites T0 and Tsp. Arrows indicate start sites and direction of transcription. The coding region contains 5′ and 3′ external transcribed spacer (ETS) and two internal transcribed spacer (ITS) regions, along with regions encoding 18S, 5.8S and 28S rRNAs. Terminator elements (T1-10) downstream of the 47S rRNA gene are also indicated. The lower panel illustrates the layout of the 47S rRNA promoter, which directs the assembly of the Pol I PIC and consists of an upstream control element, and a core promoter element overlapping the transcription start site.

Fig. 10.2

Fig. 10.2. The mammalian Pol I pre-initiation complex

Activated transcription by Pol I requires the assembly of Pol I-specific transcription factors SL1 and UBF at the rRNA promoter. In addition to contacts made between these transcription factors and the rDNA, several protein-protein interactions are also known to facilitate PIC assembly, as indicated by double-headed arrows (described in the text). A multitude of other factors cooperate with this transcription machinery to enhance PIC assembly and promote efficient rRNA synthesis by Pol I in vivo.

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