Abstract
tRNA genes are transcribed by RNA polymerase III (RNAPIII). During recent years it has become clear that RNAPIII activity is strictly regulated by the cell in response to environmental cues and the homeostatic status of the cell. However, the molecular mechanisms that control RNAPIII activity to regulate the amplitude of tDNA transcription in normally cycling cells are not well understood. Here, we show that tRNA levels fluctuate during the cell cycle and reveal an underlying molecular mechanism. The cyclin Clb5 recruits the cyclin dependent kinase Cdk1 to tRNA genes to boost tDNA transcription during late S phase. At tDNA genes, Cdk1 promotes the recruitment of TFIIIC, stimulates the interaction between TFIIIB and TFIIIC, and increases the dynamics of RNA polymerase III in vivo. Furthermore, we identified Bdp1 as a putative Cdk1 substrate in this process. Preventing Bdp1 phosphorylation prevented cell cycle-dependent recruitment of TFIIIC and abolished the cell cycle-dependent increase in tDNA transcription. Our findings demonstrate that under optimal growth conditions Cdk1 gates tRNA synthesis in S phase by regulating the RNAPIII machinery, revealing a direct link between the cell cycle and RNAPIII activity.
Highlights
The cyclin dependent kinase Cdk1 is the master regulator of the cell cycle in Saccharomyces cerevisiae
Using ChIP-seq we have previously shown that Cdk1 localizes to at least 200 genes to promote their transcription during cell cycle progression [2]
Careful inspection of the data revealed that most of these ORFs were located in close proximity to tRNA genes or snoRNAs
Summary
The cyclin dependent kinase Cdk ( known as Cdc28) is the master regulator of the cell cycle in Saccharomyces cerevisiae. Cdk associates with nine different cyclins to execute the various stages of the cell cycle. Cdk is to activate cell cycle-dependent transcriptional programs by regulating the activity of various transcription factors [1]. We and others have shown that Cdk regulates the basal transcription machinery of RNA polymerase II (RNAP II) to stimulate the expression of many housekeeping genes upon cell cycle entry [2,3], which may be important for sustaining homeostasis as the cell forms a bud and expands its volume. In addition to Cdk, numerous other factors have been identified that affect cell cycle progression. Whereas regulation of tRNA synthesis under conditions of cell stress has been relatively well studied [7], exactly how tRNA synthesis is regulated in unperturbed, cycling cells is less well understood
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