scholarly journals The GATA transcription factor Gaf1 represses tRNA genes, inhibits growth, and extends chronological lifespan downstream of fission yeast TORC1

2019 ◽  
Author(s):  
María Rodríguez-López ◽  
Suam Gonzalez ◽  
Olivia Hillson ◽  
Edward Tunnacliffe ◽  
Sandra Codlin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Rna Polymerase ◽  
Fission Yeast ◽  
Rna Polymerase Iii ◽  
Protein Translation ◽  
Trna Genes ◽  
Chronological Lifespan ◽  
Polymerase Iii ◽  
Gata Transcription Factor

AbstractTarget of Rapamycin Complex 1 (TORC1) signaling promotes growth and ageing. Inhibition of TORC1 leads to a down-regulation of factors that stimulate protein translation, including RNA polymerase III, which in turn contributes to longevity. TORC1-mediated post-transcriptional regulation of protein translation has been well studied, while analogous transcriptional regulation is less well understood. Here we screened fission yeast deletion mutants for resistance to Torin1, which inhibits TORC1 and cell growth. Mutants lacking the GATA transcription factor Gaf1 (gaf1Δ) grew normally even in high doses of Torin1. The gaf1Δ mutants shortened the chronological lifespan of non-dividing cells and diminished the lifespan extension triggered by Torin1 treatment. Expression profiling and genome-wide binding experiments showed that, after TORC1 inhibition, Gaf1 directly up-regulated genes for small-molecule metabolic pathways and indirectly repressed genes for protein translation. Surprisingly, Gaf1 bound to, and down-regulated the tRNA genes, so also functions as a transcription factor for genes transcribed by RNA polymerase III. We conclude that Gaf1 controls the transcription of both coding and tRNA genes to inhibit translation and growth downstream of TORC1.

scholarly journals Involvement of RNA Polymerase III in Immune Responses

2015 ◽  
Vol 35 (10) ◽  
pp. 1848-1859 ◽  
Author(s):  
Damian Graczyk ◽  
Robert J. White ◽  
Kevin M. Ryan
Keyword(s):  
Transcription Factor ◽  
Immune Responses ◽  
Rna Polymerase ◽  
Rna Polymerase Iii ◽  
Trna Genes ◽  
Malignant Cells ◽  
Polymerase Iii ◽  
Mouse Macrophages ◽  
Tightly Coupled ◽  
Pol Iii

Inflammation in the tumor microenvironment has many tumor-promoting effects. In particular, tumor-associated macrophages (TAMs) produce many cytokines which can support tumor growth by promoting survival of malignant cells, angiogenesis, and metastasis. Enhanced cytokine production by TAMs is tightly coupled with protein synthesis. In turn, translation of proteins depends on tRNAs, short abundant transcripts that are made by RNA polymerase III (Pol III). Here, we connect these facts by showing that stimulation of mouse macrophages with lipopolysaccharides (LPS) from the bacterial cell wall causes transcriptional upregulation of tRNA genes. The transcription factor NF-κB is a key transcription factor mediating inflammatory signals, and we report that LPS treatment causes an increased association of the NF-κB subunit p65 with tRNA genes. In addition, we show that p65 can directly associate with the Pol III transcription factor TFIIIB and that overexpression of p65 induces Pol III-dependent transcription. As a consequence of these effects, we show that inhibition of Pol III activity in macrophages restrains cytokine secretion and suppresses phagocytosis, two key functional characteristics of these cells. These findings therefore identify a radical new function for Pol III in the regulation of macrophage function which may be important for the immune responses associated with both normal and malignant cells.

scholarly journals Role of RNA Polymerase III Transcription Factors in the Selection of Integration Sites by the Dictyostelium Non-Long Terminal Repeat Retrotransposon TRE5-A

2006 ◽  
Vol 26 (22) ◽  
pp. 8242-8251 ◽  
Author(s):  
Oliver Siol ◽  
Moustapha Boutliliss ◽  
Thanh Chung ◽  
Gernot Glöckner ◽  
Theodor Dingermann ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Rna Polymerase ◽  
Long Terminal Repeat ◽  
Integration Site ◽  
Rna Polymerase Iii ◽  
Terminal Repeat ◽  
Trna Genes ◽  
Ltr Retrotransposons ◽  
Polymerase Iii

ABSTRACT In the compact Dictyostelium discoideum genome, non-long terminal repeat (non-LTR) retrotransposons known as TREs avoid accidental integration-mediated gene disruption by targeting the vicinity of tRNA genes. In this study we provide the first evidence that proteins of a non-LTR retrotransposon interact with a target-specific transcription factor to direct its integration. We applied an in vivo selection system that allows for the isolation of natural TRE5-A integrations into a known genomic location upstream of tRNA genes. TRE5-A frequently modified the integration site in a way characteristic of other non-LTR retrotransposons by adding nontemplated extra nucleotides and generating small and extended target site deletions. Mutations within the B-box promoter of the targeted tRNA genes interfered with both the in vitro binding of RNA polymerase III transcription factor TFIIIC and the ability of TRE5-A to target these genes. An isolated B box was sufficient to enhance TRE5-A integration in the absence of a surrounding tRNA gene. The RNA polymerase III-transcribed ribosomal 5S gene recruits TFIIIC in a B-box-independent manner, yet it was readily targeted by TRE5-A in our assay. These results suggest a direct role of an RNA polymerase III transcription factor in the targeting process.

scholarly journals Determinants of Replication-Fork Pausing at tRNA Genes in Saccharomyces cerevisiae

Genetics ◽  
2020 ◽  
Vol 214 (4) ◽  
pp. 825-838
Author(s):  
Rani Yeung ◽  
Duncan J. Smith
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Repair ◽  
Transcription Factor ◽  
Rna Polymerase ◽  
Replication Fork ◽  
Rna Polymerase Iii ◽  
Trna Genes ◽  
Link Type ◽  
Replication Fork Progression ◽  
Polymerase Iii

Transfer RNA (tRNA) genes are widely studied sites of replication-fork pausing and genome instability in the budding yeast Saccharomyces cerevisiae. tRNAs are extremely highly transcribed and serve as constitutive condensin binding sites. tRNA transcription by RNA polymerase III has previously been identified as stimulating replication-fork pausing at tRNA genes, but the nature of the block to replication has not been incontrovertibly demonstrated. Here, we describe a systematic, genome-wide analysis of the contributions of candidates to replication-fork progression at tDNAs in yeast: transcription factor binding, transcription, topoisomerase activity, condensin-mediated clustering, and Rad18-dependent DNA repair. We show that an asymmetric block to replication is maintained even when tRNA transcription is abolished by depletion of one or more subunits of RNA polymerase III. By contrast, analogous depletion of the essential transcription factor TFIIIB removes the obstacle to replication. Therefore, our data suggest that the RNA polymerase III transcription complex itself represents an asymmetric obstacle to replication even in the absence of RNA synthesis. We additionally demonstrate that replication-fork progression past tRNA genes is unaffected by the global depletion of condensin from the nucleus, and can be stimulated by the removal of topoisomerases or Rad18-dependent DNA repair pathways.

scholarly journals The impediment to replication at tRNA genes in S. cerevisiae does not require tRNA transcription, and is facilitated by topoisomerases and Rad18-dependent repair pathways

2020 ◽  
Author(s):  
Rani Yeung ◽  
Duncan J. Smith
Keyword(s):  
Dna Repair ◽  
Transcription Factor ◽  
Rna Polymerase ◽  
Replication Fork ◽  
Genome Instability ◽  
Rna Polymerase Iii ◽  
Trna Genes ◽  
Replication Fork Progression ◽  
Polymerase Iii ◽  
Repair Pathways

ABSTRACTtRNA genes are widely studied sites of replication-fork pausing and genome instability in the budding yeast Saccharomyces cerevisiae. tRNAs are extremely highly transcribed and serve as constitutive condensin binding sites. tRNA transcription by RNA polymerase III has previously been identified as stimulating replication-fork pausing at tRNA genes, but the nature of the block to replication has not been incontrovertibly demonstrated. Here, we describe a systematic, genome-wide analysis of the contributions of candidates to replication-fork progression at tDNAs in yeast: transcription factor binding, transcription, topoisomerase activity, condensin-mediated clustering, and Rad18-dependent DNA repair. We show that an asymmetric block to replication is maintained even when tRNA transcription is abolished by depletion of one or more subunits of RNA polymerase III. By contrast, analogous depletion of the essential transcription factor TFIIIB removes the obstacle to replication. Therefore, our data suggest that the RNA polymerase III transcription complex itself represents an asymmetric obstacle to replication even in the absence of RNA synthesis. We additionally demonstrate that replication-fork progression past tRNA genes is unaffected by the global depletion of condensin from the nucleus, and can be stimulated by the removal of topoisomerases or Rad18-dependent DNA repair pathways.

scholarly journals Transcription-independent TFIIIC-bound sites cluster near heterochromatin boundaries within lamina-associated domains in C. elegans

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Alexis V. Stutzman ◽  
April S. Liang ◽  
Vera Beilinson ◽  
Kohta Ikegami
Keyword(s):  
Transcription Factor ◽  
Rna Polymerase ◽  
Mammalian Cells ◽  
Sex Chromosome ◽  
Rna Polymerase Iii ◽  
Chromatin Organization ◽  
Control Of Gene Expression ◽  
C Elegans ◽  
Polymerase Iii ◽  
The Individual

Abstract Background Chromatin organization is central to precise control of gene expression. In various eukaryotic species, domains of pervasive cis-chromatin interactions demarcate functional domains of the genomes. In nematode Caenorhabditis elegans, however, pervasive chromatin contact domains are limited to the dosage-compensated sex chromosome, leaving the principle of C. elegans chromatin organization unclear. Transcription factor III C (TFIIIC) is a basal transcription factor complex for RNA polymerase III, and is implicated in chromatin organization. TFIIIC binding without RNA polymerase III co-occupancy, referred to as extra-TFIIIC binding, has been implicated in insulating active and inactive chromatin domains in yeasts, flies, and mammalian cells. Whether extra-TFIIIC sites are present and contribute to chromatin organization in C. elegans remains unknown. Results We identified 504 TFIIIC-bound sites absent of RNA polymerase III and TATA-binding protein co-occupancy characteristic of extra-TFIIIC sites in C. elegans embryos. Extra-TFIIIC sites constituted half of all identified TFIIIC binding sites in the genome. Extra-TFIIIC sites formed dense clusters in cis. The clusters of extra-TFIIIC sites were highly over-represented within the distal arm domains of the autosomes that presented a high level of heterochromatin-associated histone H3K9 trimethylation (H3K9me3). Furthermore, extra-TFIIIC clusters were embedded in the lamina-associated domains. Despite the heterochromatin environment of extra-TFIIIC sites, the individual clusters of extra-TFIIIC sites were devoid of and resided near the individual H3K9me3-marked regions. Conclusion Clusters of extra-TFIIIC sites were pervasive in the arm domains of C. elegans autosomes, near the outer boundaries of H3K9me3-marked regions. Given the reported activity of extra-TFIIIC sites in heterochromatin insulation in yeasts, our observation raised the possibility that TFIIIC may also demarcate heterochromatin in C. elegans.

scholarly journals An RNA Polymerase III-Dependent Heterochromatin Barrier at Fission Yeast Centromere 1

PLoS ONE ◽  
2007 ◽  
Vol 2 (10) ◽  
pp. e1099 ◽  
Author(s):  
Kristin C. Scott ◽  
Caroline V. White ◽  
Huntington F. Willard
Keyword(s):  
Rna Polymerase ◽  
Fission Yeast ◽  
Rna Polymerase Iii ◽  
Polymerase Iii
Sign in / Sign up

Export Citation Format

Share Document