Ras/ERK-signalling promotes tRNA synthesis and growth via the RNA polymerase III repressor Maf1 in Drosophila

Sriskanthadevan-Pirahas, Shrivani; Deshpande, Rujuta; Lee, Byoungchun; Grewal, Savraj

doi:10.1371/journal.pgen.1007202

Cited by 31 publications

(17 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another important marker change indicating activation of NF-κB is Polr3a, which has been shown to induce IFN-I 44 . Furthermore, the function of Pol III is promoted by activated Ras signaling 127 . Upregulation of these markers was observed in all treatments, but similar to the markers of NF-κB suppression, it was most significant in DWV_VAR.…”

Section: Resultsmentioning

confidence: 99%

Varroa destructor parasitism has a greater effect on proteome changes than the deformed wing virus and activates TGF-β signaling pathways

Erban

Sopko

Kadlikova

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Honeybee workers undergo metamorphosis in capped cells for approximately 13 days before adult emergence. During the same period, Varroa mites prick the defenseless host many times. We sought to identify proteome differences between emerging Varroa -parasitized and parasite-free honeybees showing the presence or absence of clinical signs of deformed wing virus ( DWV ) in the capped cells. A label-free proteomic analysis utilizing nanoLC coupled with an Orbitrap Fusion Tribrid mass spectrometer provided a quantitative comparison of 2316 protein hits. Redundancy analysis (RDA) showed that the combination of Varroa parasitism and DWV clinical signs caused proteome changes that occurred in the same direction as those of Varroa alone and were approximately two-fold higher. Furthermore, proteome changes associated with DWV signs alone were positioned above Varroa in the RDA. Multiple markers indicate that Varroa activates TGF-β-induced pathways to suppress wound healing and the immune response and that the collective action of stressors intensifies these effects. Furthermore, we indicate JAK/STAT hyperactivation, p53-BCL-6 feedback loop disruption, Wnt pathway activation, Wnt/Hippo crosstalk disruption, and NF-κB and JAK/STAT signaling conflict in the Varroa –honeybee– DWV interaction. These results illustrate the higher effect of Varroa than of DWV at the time of emergence. Markers for future research are provided.

show abstract

Section: Resultsmentioning

confidence: 99%

Varroa destructor parasitism has a greater effect on proteome changes than the deformed wing virus and activates TGF-β signaling pathways

Erban

Sopko

Kadlikova

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…It has been documented that many clinical cancer specimens contain aberrantly high levels of TFIIIB or GTF3C2 (1,10,11). Nutrients, signaling pathway factors, and chromatin modifiers are also involved in the regulation of Pol III gene transcription (3,8,(12)(13)(14). However, the regulatory mechanisms of Pol III gene transcription in human cancer cells are not fully understood.…”

mentioning

confidence: 99%

The transcription factor Sp1 modulates RNA polymerase III gene transcription by controlling BRF1 and GTF3C2 expression in human cells

Peng

Zhou

Wang

et al. 2020

Journal of Biological Chemistry

View full text Add to dashboard Cite

Specificity protein 1 (Sp1) is an important transcription factor implicated in numerous cellular processes. However, whether Sp1 is involved in the regulation of RNA polymerase III (Pol III)-directed gene transcription in human cells remains unknown. Here, we first show that filamin A (FLNA) represses Sp1 expression as well as expression of TFIIB-related factor 1 (BRF1) and general transcription factor III C subunit 2 (GTF3C2) in HeLa, 293T, and SaOS2 cell lines stably expressing FLNA-silencing shRNAs. Both BRF1 promoter 4 (BRF1P4) and GTF3C2 promoter 2 (GTF3C2P2) contain putative Sp1-binding sites, suggesting that Sp1 affects Pol III gene transcription by regulating BRF1 and GTF3C2 expression. We demonstrate that Sp1 knockdown inhibits Pol III gene transcription, BRF1 and GTF3C2 expression, and the proliferation of 293T and HeLa cells, whereas Sp1 overexpression enhances these activities. We obtained a comparable result in a cell line in which both FLNA and Sp1 were depleted. These results indicate that Sp1 is involved in the regulation of Pol III gene transcription independently of FLNA expression. Reporter gene assays showed that alteration of Sp1 expression affects BRF1P4 and GTF3C2P2 activation, suggesting that Sp1 modulates Pol III–mediated gene transcription by controlling BRF1 and GTF3C2 gene expression. Further analysis revealed that Sp1 interacts with and thereby promotes the occupancies of TATA box–binding protein, TFIIAα, and p300 at both BRF1P4 and GTF3C2P2. These findings indicate that Sp1 controls Pol III–directed transcription and shed light on how Sp1 regulates cancer cell proliferation.

show abstract

“…This may be due to tissue specific differences in Pol-III regulation or a role for mutant Kras in tRNA transcription. Mutant Ras promotes tRNA synthesis via Brf1 in Drosophila [56], providing a possible explanation for the enhanced tRNA transcription in BRF1 over-expressing, Kras mutant pancreata.…”

Section: Resultsmentioning

confidence: 99%

Brf1 loss and not overexpression disrupts tissues homeostasis in the intestine, liver and pancreas

et al. 2019

View full text Add to dashboard Cite

RNA polymerase III (Pol-III) transcribes tRNAs and other small RNAs essential for protein synthesis and cell growth. Pol-III is deregulated during carcinogenesis; however, its role in vivo has not been studied. To address this issue, we manipulated levels of Brf1, a Pol-III transcription factor that is essential for recruitment of Pol-III holoenzyme at tRNA genes in vivo. Knockout of Brf1 led to embryonic lethality at blastocyst stage. In contrast, heterozygous Brf1 mice were viable, fertile and of a normal size. Conditional deletion of Brf1 in gastrointestinal epithelial tissues, intestine, liver and pancreas, was incompatible with organ homeostasis. Deletion of Brf1 in adult intestine and liver induced apoptosis. However, Brf1 heterozygosity neither had gross effects in these epithelia nor did it modify tumorigenesis in the intestine or pancreas. Overexpression of BRF1 rescued the phenotypes of Brf1 deletion in intestine and liver but was unable to initiate tumorigenesis. Thus, Brf1 and Pol-III activity are absolutely essential for normal homeostasis during development and in adult epithelia. However, Brf1 overexpression or heterozygosity are unable to modify tumorigenesis, suggesting a permissive, but not driving role for Brf1 in the development of epithelial cancers of the pancreas and gut.

show abstract

Ras/ERK-signalling promotes tRNA synthesis and growth via the RNA polymerase III repressor Maf1 in Drosophila

Cited by 31 publications

References 74 publications

Varroa destructor parasitism has a greater effect on proteome changes than the deformed wing virus and activates TGF-β signaling pathways

Varroa destructor parasitism has a greater effect on proteome changes than the deformed wing virus and activates TGF-β signaling pathways

The transcription factor Sp1 modulates RNA polymerase III gene transcription by controlling BRF1 and GTF3C2 expression in human cells

Brf1 loss and not overexpression disrupts tissues homeostasis in the intestine, liver and pancreas

Contact Info

Product

Resources

About