Novel layers of RNA polymerase III control affecting tRNA gene transcription in eukaryotes

Leśniewska, Ewa; Boguta, Magdalena

doi:10.1098/rsob.170001

Cited by 44 publications

(34 citation statements)

References 111 publications

(241 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We thus postulated that Rbs1 protein functions as an assembly/import factor for the Pol III complex [10]. Numerous previous studies concerning the biogenesis of multi-subunit RNA polymerases suggest that the Pol III complex is assembled in the cytoplasm with the help of assembly factors and then transported to the nucleus where it transcribes tRNA genes (reviewed in [13,14]).…”

Section: Introductionmentioning

confidence: 98%

Coupling of RNA polymerase III assembly to cell cycle progression in Saccharomyces cerevisiae

et al. 2019

Self Cite

View full text Add to dashboard Cite

Assembly of the RNA polymerases in both yeast and humans is proposed to occur in the cytoplasm prior to their nuclear import. Our previous studies identified a cold-sensitive mutation, rpc128-1007, in the yeast gene encoding the second largest Pol III subunit, Rpc128. rpc128-1007 is associated with defective assembly of Pol III complex and, in consequence, decreased level of tRNA synthesis. Here, we show that rpc128-1007 mutant cells remain largely unbudded and larger than wild type cells. Flow cytometry revealed that most rpc128-1007 mutant cells have G1 DNA content, suggesting that this mutation causes pronounced cell cycle delay in the G1 phase. Increased expression of gene encoding Rbs1, the Pol III assembly/import factor, could counteract G1 arrest observed in the rpc128-1007 mutant and restore wild type morphology of mutant cells. Concomitantly, cells lacking Rbs1 show a mild delay in G1 phase exit, indicating that Rbs1 is required for timely cell cycle progression. Using the double rpc128-1007 maf1Δ mutant in which tRNA synthesis is recovered, we confirmed that the Pol III assembly defect associated with rpc128-1007 is a primary cause of cell cycle arrest. Together our results indicate that impairment of Pol III complex assembly is coupled to cell cycle inhibition in the G1 phase. ARTICLE HISTORY

show abstract

Section: Introductionmentioning

confidence: 98%

Coupling of RNA polymerase III assembly to cell cycle progression in Saccharomyces cerevisiae

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Pol III transcription is hence tightly regulated in response to stress and growth signals, and several signaling pathways converge to modulate the function of the Pol III machinery including its central negative regulator, Maf 2,6 . Maf1 is conserved across eukaryotes, and has been studied in yeast, flies, worms, plants, parasites and mammalian systems (reviewed in 7,8 ). Recently, it was demonstrated that overexpression of Maf1 in the gut of flies increases the lifespan of these animals 9 .…”

Section: Introductionmentioning

confidence: 99%

Structural basis of RNA polymerase III transcription repression by Maf1

Vorländer¹,

Baudin²,

Moir³

et al. 2019

Preprint

View full text Add to dashboard Cite

Maf1 is a highly conserved central regulator of transcription by RNA polymerase III (Pol III), and Maf1 activity influences a wide range of phenotypes from metabolic efficiency to lifespan. Here, we present a 3.3 Å cryo-EM structure of yeast Maf1 bound to Pol III, which establishes how Maf1 achieves transcription repression. In the Maf1-bound state, Pol III elements that are involved in transcription initiation are sequestered, and the active site is sealed off due to ordering of the mobile C34 winged helix 2 domain. Specifically, the Maf1 binding site overlaps with the binding site of the Pol III transcription factor TFIIIB and DNA in the pre-initiation complex, rationalizing that binding of Maf1 and TFIIIB to Pol III are mutually exclusive. We validate our structure using variants of Maf1 with impaired transcription-inhibition activity. These results reveal the exact mechanism of Pol III inhibition by Maf1, and rationalize previous biochemical data.

show abstract

“…Given the importance of Pol III in the response to stress (12), we assessed the genome occupancy of TFIIIC in T47D breast cancer cells growing in normal condition (+S) and after 16 Ferrari et al 2019 4 h of SS (-S) ( fig. S1A), which did not alter significantly the cell cycle profile (fig.…”

Section: Introductionmentioning

confidence: 99%

TFIIIC binding to Alu elements controls gene expression via chromatin looping and histone acetylation

Ferrari

Cucalon

Vona

et al. 2018

Preprint

View full text Add to dashboard Cite

The mammalian genome is shaped by the expansion of repetitive elements and its folding is governed by epigenetic modifications and architectural proteins. However, the precise way all these factors interact to coordinate genome structure and expression is poorly understood. Here we report that upon serum starvation TFIIIC, a general transcription factor, binds a subset of Alu elements close to cell cycle genes and rewires genome topology via direct histone acetylation and promoter-anchored chromatin loops to distant genes. These changes ensure basal transcription of crucial cell cycle genes and their re-activation upon serum re-exposure. Our study unveils a novel function of TFIIIC on gene expression and genome folding achieved through casting direct manipulation of the epigenetic state of Alu elements to adjust 3D genome function.

show abstract

Novel layers of RNA polymerase III control affecting tRNA gene transcription in eukaryotes

Cited by 44 publications

References 111 publications

Coupling of RNA polymerase III assembly to cell cycle progression in Saccharomyces cerevisiae

Coupling of RNA polymerase III assembly to cell cycle progression in Saccharomyces cerevisiae

Structural basis of RNA polymerase III transcription repression by Maf1

TFIIIC binding to Alu elements controls gene expression via chromatin looping and histone acetylation

Contact Info

Product

Resources

About