scholarly journals Mitochondrial ubiquinone–mediated longevity is marked by reduced cytoplasmic mRNA translation

2018 ◽  
Vol 1 (5) ◽  
pp. e201800082 ◽  
Author(s):  
Marte Molenaars ◽  
Georges E Janssens ◽  
Toon Santermans ◽  
Marco Lezzerini ◽  
Rob Jelier ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Transcription Initiation ◽  
Binding Protein ◽  
Mrna Translation ◽  
Tata Binding Protein ◽  
Early Embryogenesis ◽  
Life Extension ◽  
Initiation Factor ◽  
Associated Factor ◽  
Transcription Initiation Factor

Mutations in the clk-1 gene impair mitochondrial ubiquinone biosynthesis and extend the lifespan in Caenorhabditis elegans. We demonstrate here that this life extension is linked to the repression of cytoplasmic mRNA translation, independent of the alleged nuclear form of CLK-1. Clk-1 mutations inhibit polyribosome formation similarly to daf-2 mutations that dampen insulin signaling. Comparisons of total versus polysomal RNAs in clk-1(qm30) mutants reveal a reduction in the translational efficiencies of mRNAs coding for elements of the translation machinery and an increase in those coding for the oxidative phosphorylation and autophagy pathways. Knocking down the transcription initiation factor TATA-binding protein-associated factor 4, a protein that becomes sequestered in the cytoplasm during early embryogenesis to induce transcriptional silencing, ameliorates the clk-1 inhibition of polyribosome formation. These results underscore a prominent role for the repression of cytoplasmic protein synthesis in eukaryotic lifespan extension and suggest that mutations impairing mitochondrial function are able to exploit this repression similarly to reductions of insulin signaling. Moreover, this report reveals an unexpected role for TATA-binding protein-associated factor 4 as a repressor of polyribosome formation when ubiquinone biosynthesis is compromised.

scholarly journals Mitochondrial ubiquinone-mediated longevity is marked by reduced cytoplasmic protein translation

2018 ◽  
Author(s):  
Marte Molenaars ◽  
Georges E. Janssens ◽  
Toon Santermans ◽  
Marco Lezzerini ◽  
Rob Jelier ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Transcription Initiation ◽  
Transcriptional Silencing ◽  
Protein Translation ◽  
Early Embryogenesis ◽  
Life Extension ◽  
Initiation Factor ◽  
Cytoplasmic Protein ◽  
C Elegans ◽  
Transcription Initiation Factor

AbstractMutations in the clk-1 gene impair mitochondrial ubiquinone biosynthesis and extend the lifespan of C. elegans. We demonstrate here that this life extension is linked to the repression of cytoplasmic protein translation. Clk-1 mutations inhibit polyribosome formation similarly to daf-2 mutations that dampen insulin signaling. Comparisons of total versus polysomal RNAs in clk-1 mutants reveal a reduction in the translational efficiencies of mRNAs coding for elements of the translation machinery and an increase in those coding for the oxidative phosphorylation and autophagy pathways. Knocking down the transcription initiation factor TAF-4, a protein that becomes sequestered in the cytoplasm during early embryogenesis to induce transcriptional silencing, ameliorates the clk-1 inhibition of polyribosome formation. These results underscore a prominent role for the repression of cytoplasmic protein translation in eukaryotic lifespan extension, and suggest that mutations impairing mitochondrial function are able to exploit this repression similarly to reductions of insulin signaling. Moreover, this report reveals an unexpected role for TAF-4 as a repressor of polyribosome formation when ubiquinone biosynthesis is compromised.

scholarly journals Inhibition of TATA Binding Protein Dimerization by RNA Polymerase III Transcription Initiation Factor Brf1

2004 ◽  
Vol 279 (31) ◽  
pp. 32401-32406 ◽  
Author(s):  
Diane E. Alexander ◽  
David J. Kaczorowski ◽  
Amy J. Jackson-Fisher ◽  
Drew M. Lowery ◽  
Sara J. Zanton ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Transcription Initiation ◽  
Binding Protein ◽  
Rna Polymerase Iii ◽  
Tata Binding Protein ◽  
Initiation Factor ◽  
Protein Dimerization ◽  
Polymerase Iii ◽  
Transcription Initiation Factor

scholarly journals The TATA-Binding Protein (TBP) from the Human Fungal PathogenCandida albicans Can Complement Defects in Human and Yeast TBPs

1998 ◽  
Vol 180 (7) ◽  
pp. 1771-1776 ◽  
Author(s):  
Ping Leng ◽  
Philip E. Carter ◽  
Alistair J. P. Brown
Keyword(s):  
Amino Acid ◽  
Dna Binding ◽  
Transcription Initiation ◽  
Binding Protein ◽  
Tata Binding Protein ◽  
Binding Domain ◽  
Amino Acid Sequences ◽  
Initiation Factor ◽  
Dna Binding Domain

ABSTRACT Candida albicans is the major fungal pathogen in humans, yet little is known about transcriptional regulation in this organism. Therefore, we have isolated, characterized, and expressed theC. albicans TATA-binding protein (TBP) gene (TBP1), because this general transcription initiation factor plays a key role in the activation and regulation of eukaryotic promoters. Southern and Northern blot analyses suggest that a single C. albicans TBP1 locus is expressed at similar levels in the yeast and hyphal forms of this fungus. The TBP1 open reading frame is 716 bp long and encodes a functional TBP of 27 kDa. C. albicans TBP is capable of binding specifically to a TATA box in vitro, substituting for the human TBP to activate basal transcription in vitro, and suppressing the lethal Δspt15 mutation inSaccharomyces cerevisiae. The predicted amino acid sequences of TBPs from C. albicans and other organisms reveal a striking pattern of C-terminal conservation and N-terminal variability: the C-terminal DNA-binding domain displays at least 80% amino acid sequence identity to TBPs from fungi, flies, nematodes, slime molds, plants, and humans. Sequence differences between human and fungal TPBs in the DNA-binding domain may represent potential targets for antifungal therapy.

TATA box-binding protein (TBP) is a constituent of the polymerase I-specific transcription initiation factor TIF-IB (SL1) bound to the rRNA promoter and shows differential sensitivity to TBP-directed reagents in polymerase I, II, and III transcription factors

1994 ◽  
Vol 14 (1) ◽  
pp. 597-605
Author(s):  
C A Radebaugh ◽  
J L Matthews ◽  
G K Geiss ◽  
F Liu ◽  
J M Wong ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Binding Protein ◽  
Acanthamoeba Castellanii ◽  
Differential Sensitivity ◽  
Initiation Factor ◽  
Transcription Initiation Factor ◽  
I Factor ◽  
Tata Box Binding Protein ◽  
Polymerase I

The role of the Acanthamoeba castellanii TATA-binding protein (TBP) in transcription was examined. Specific antibodies against the nonconserved N-terminal domain of TBP were used to verify the presence of TBP in the fundamental transcription initiation factor for RNA polymerase I, TIF-IB, and to demonstrate that TBP is part of the committed initiation complex on the rRNA promoter. The same antibodies inhibit transcription in all three polymerase systems, but they do so differentially. Oligonucleotide competitors were used to evaluate the accessibility of the TATA-binding site in TIF-IB, TFIID, and TFIIIB. The results suggest that insertion of TBP into the polymerase II and III factors is more similar than insertion into the polymerase I factor.

252. Regulated nuclear import of TATA binding protein associated factor 9 (TAF9) in spermatogenesis

2008 ◽  
Vol 20 (9) ◽  
pp. 52 ◽  
Author(s):  
S. B. Prakash ◽  
J. D. Ly-Huynh ◽  
K. L. Loveland ◽  
D. A. Jans
Keyword(s):  
Nuclear Import ◽  
Transcription Initiation ◽  
Binding Protein ◽  
Core Promoter ◽  
Late Phase ◽  
Tata Binding Protein ◽  
Associated Factor ◽  
Immunohistochemistry Staining ◽  
Dependent Transport ◽  
And Function

Spermatogenesis, the differentiation process resulting in the production of haploid germ cells able to fertilise an oocyte, is driven by nuclear transcription factors, and changes in nuclear morphology and function itself. Signal-dependent transport into and out of the nucleus is mediated by members of the importin (IMP) superfamily of transporters, which we have previously shown to change dynamically in expression profile during spermatogenesis. One IMP family member, IMPα2, is expressed during mid to late phase spermatogenesis, implying that it may transport specific cargoes important for these stages, with a potential cargo of significance identified in a yeast 2-hybrid screen being TAF9 (TATA-Binding Protein Associated Factor 9). TAF9 is an integral part of transcription initiation for many genes, such as those with a Downstream Promoter Element in the core promoter and those with activators such as SOX18, p53, HSF1, NF-IL6 or NF-κB. In addition it participates in histone acetylation complexes which have been previously described to be important for the completion of spermatogenesis. Our preliminary data confirm the interaction of IMPα2 and TAF9 using a cotransfection approach. We have also shown that the expression of these proteins in the testis is correlated using both publically available Affymetrix data, and immunohistochemistry staining. TAF9, like IMPα2, is expressed in the nucleus of elongating spermatids of the adult rodent testis. Our data are thus consistent with the idea that specific nuclear import of TAF9 by IMPα2 may be a critical step in the later stages of spermatogenesis.

scholarly journals Epidermal Growth Factor Receptor 1 (EGFR1) and Its Variant EGFRvIII Regulate TATA-Binding Protein Expression through Distinct Pathways

2008 ◽  
Vol 28 (20) ◽  
pp. 6483-6495 ◽  
Author(s):  
Jody A. Fromm ◽  
Sandra A. S. Johnson ◽  
Deborah L. Johnson
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Transcription Initiation ◽  
Binding Protein ◽  
Growth Factor Receptor ◽  
Tata Binding Protein ◽  
Initiation Factor ◽  
Transcriptional Level ◽  
Epidermal Growth

ABSTRACT The epidermal growth factor receptor (EGFR) family regulates essential biological processes. Various epithelial tumors are linked to EGFR overexpression or expression of variant forms, such as the EGFR1 variant, EGFRvIII. Perturbations in expression of the transcription initiation factor, TATA-binding protein (TBP), alter cellular growth properties. Here we demonstrate that EGFR1 and EGFRvIII, but not HER2, induce TBP expression at a transcriptional level through distinct mechanisms. EGFR1 enhances the phosphorylation and function of Elk-1, recruiting it to the TBP promoter. In contrast, EGFRvIII robustly induces c-jun expression, stimulating recruitment of c-fos/c-jun to an overlapping AP-1 site. Enhancing c-jun expression alone induces TBP promoter activity through the AP-1 site. To determine the underlying mechanism for differences in Elk-1 function and c-jun expression by these receptors, we inhibited the internalization of EGFR1. Persistent EGFR1 cell surface occupancy mimics EGFRvIII-mediated effects on Elk-1 and c-jun and switches the requirement of Elk-1 to AP-1 for TBP promoter induction. Together, these studies define a new molecular mechanism for the regulation of TBP expression. In addition, we identify distinct molecular targets of EGFR1 and EGFRvIII and demonstrate the importance of receptor internalization in distinguishing their specific functions.

scholarly journals TATA box-binding protein (TBP) is a constituent of the polymerase I-specific transcription initiation factor TIF-IB (SL1) bound to the rRNA promoter and shows differential sensitivity to TBP-directed reagents in polymerase I, II, and III transcription factors.

1994 ◽  
Vol 14 (1) ◽  
pp. 597-605 ◽  
Author(s):  
C A Radebaugh ◽  
J L Matthews ◽  
G K Geiss ◽  
F Liu ◽  
J M Wong ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Binding Protein ◽  
Acanthamoeba Castellanii ◽  
Differential Sensitivity ◽  
Initiation Factor ◽  
Transcription Initiation Factor ◽  
I Factor ◽  
Tata Box Binding Protein ◽  
Polymerase I

The role of the Acanthamoeba castellanii TATA-binding protein (TBP) in transcription was examined. Specific antibodies against the nonconserved N-terminal domain of TBP were used to verify the presence of TBP in the fundamental transcription initiation factor for RNA polymerase I, TIF-IB, and to demonstrate that TBP is part of the committed initiation complex on the rRNA promoter. The same antibodies inhibit transcription in all three polymerase systems, but they do so differentially. Oligonucleotide competitors were used to evaluate the accessibility of the TATA-binding site in TIF-IB, TFIID, and TFIIIB. The results suggest that insertion of TBP into the polymerase II and III factors is more similar than insertion into the polymerase I factor.

Mechanism of initiator-mediated transcription: evidence for a functional interaction between the TATA-binding protein and DNA in the absence of a specific recognition sequence

1993 ◽  
Vol 13 (7) ◽  
pp. 3841-3849
Author(s):  
B Zenzie-Gregory ◽  
A Khachi ◽  
I P Garraway ◽  
S T Smale
Keyword(s):  
Transcription Initiation ◽  
Binding Protein ◽  
Tata Binding Protein ◽  
Upstream Region ◽  
Promoter Strength ◽  
Recognition Sequence ◽  
Specific Recognition ◽  
Rate Limiting

Promoters containing Sp1 binding sites and an initiator element but lacking a TATA box direct high levels of accurate transcription initiation by using a mechanism that requires the TATA-binding protein (TBP). We have begun to address the role of TBP during transcription from Sp1-initiator promoters by varying the nucleotide sequence between -14 and -33 relative to the start site. With each of several promoters containing different upstream sequences, we detected accurate transcription both in vitro and in vivo, but the promoter strengths varied widely, particularly with the in vitro assay. The variable promoter activities correlated with, but were not proportional to, the abilities of the upstream sequences to function as TATA boxes, as assessed by multiple criteria. These results confirm that accurate transcription can proceed in the presence of an initiator, regardless of the sequence present in the -30 region. However, the results reveal a role for this upstream region, most consistent with a model in which initiator-mediated transcription requires binding of TBP to the upstream DNA in the absence of a specific recognition sequence. Moreover, in vivo it appears that the promoter strength is modulated less severely by altering the -30 sequence, consistent with a previous suggestion that TBP is not rate limiting in vivo for TATA-less promoters. Taken together, these results suggest that variations in the structure of a core promoter might alter the rate-limiting step for transcription initiation and thereby alter the potential modes of transcriptional regulation, without severely changing the pathway used to assemble a functional preinitiation complex.

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