Abstract
A prerequisite for protein synthesis is the transcription of ribosomal rRNA genes by RNA polymerase I (Pol I), which controls ribosome biogenesis. UBF (upstream binding factor) is one of the main Pol I transcription factors located in the nucleolus that activates rRNA gene transcription. E2F7 is an atypical E2F family member that acts as a transcriptional repressor of E2F target genes, and thereby contributes to cell cycle arrest. Here, we describe an unexpected role for E2F7 in regulating rRNA gene transcription. We have found that E2F7 localises to the perinucleolar region, and further that E2F7 is able to exert repressive effects on Pol I transcription. At the mechanistic level, this is achieved in part by E2F7 hindering UBF recruitment to the rRNA gene promoter region, and thereby reducing rRNA gene transcription, which in turn compromises global protein synthesis. Our results expand the target gene repertoire influenced by E2F7 to include Pol I-regulated genes, and more generally suggest a mechanism mediated by effects on Pol I transcription where E2F7 links cell cycle arrest with protein synthesis.
Highlights
The rate of protein synthesis is directly proportional to cell growth and proliferation
Since transcription factor UBF is essential for transcription by RNA Pol I21,22, we examined any effect of E2F7 on UBF recruitment to the polymerase I (Pol I) promoter, and observed a significant enhancement in the recruitment of UBF to the rRNA gene promoter region after E2F7 depletion (Fig. 3c)
Cancer cells are by nature rapidly dividing and as such require elevated protein production mediated by enhanced rRNA gene transcription and Pol I activity[28]
Summary
The rate of protein synthesis is directly proportional to cell growth and proliferation. This is, in turn, intimately linked to ribosome biogenesis, which is controlled at the transcription level by Pol I1. The Pol I transcription machinery integrates information from cellular signalling cascades to regulate ribosome production and this guides cell growth and proliferation[1]. Ribosome biogenesis occurs in the nucleolus, and transcription of rRNA genes by Pol I is a major point of control. Pol I accounts for up to 60% of transcriptional activity in the cell, and rRNA contributes for up to 80% of the total RNA2. Ribosome biosynthesis consumes about 80% of a cell’s
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