Direct Regulation of tRNA and 5S rRNA Gene Transcription by Polo-like Kinase 1

SummaryPolo-like kinase Plk1 controls numerous aspects of cell-cycle progression. We show that it associates with tRNA and 5S rRNA genes and regulates their transcription by RNA polymerase III (pol III) through direct binding and phosphorylation of transcription factor Brf1. During interphase, Plk1 promotes tRNA and 5S rRNA expression by phosphorylating Brf1 directly on serine 450. However, this stimulatory modification is overridden at mitosis, when elevated Plk1 activity causes Brf1 phosphorylation on threonine 270 (T270), which prevents pol III recruitment. Thus, although Plk1 enhances net tRNA and 5S rRNA production, consistent with its proliferation-stimulating function, it also suppresses untimely transcription when cells divide. Genomic instability is apparent in cells with Brf1 T270 mutated to alanine to resist Plk1-directed inactivation, suggesting that chromosome segregation is vulnerable to inappropriate pol III activity.

► Transcription by pol III of tRNA and 5S rRNA genes is regulated directly by Plk1
► Plk1 stimulates pol III transcription in interphase by phosphorylating Brf1 on S450
► At mitosis, Plk1 causes repression through Brf1 phosphorylation on T270
► T270A mutation of Brf1 results in mitotic abnormalities