scholarly journals DNA damage regulates direct association of TOR kinase with the RNA polymerase II–transcribed HMO1 gene

2017 ◽  
Vol 28 (18) ◽  
pp. 2449-2459 ◽  
Author(s):  
Arvind Panday ◽  
Ashish Gupta ◽  
Kavitha Srinivasa ◽  
Lijuan Xiao ◽  
Mathew D. Smith ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
High Mobility ◽  
Gene Activity ◽  
High Mobility Group Protein ◽  
Down Regulation ◽  
Direct Association ◽  
Tor Kinase

The mechanistic target of rapamycin complex 1 (mTORC1) senses nutrient sufficiency and cellular stress. When mTORC1 is inhibited, protein synthesis is reduced in an intricate process that includes a concerted down-regulation of genes encoding rRNA and ribosomal proteins. The Saccharomyces cerevisiae high-mobility group protein Hmo1p has been implicated in coordinating this response to mTORC1 inhibition. We show here that Tor1p binds directly to the HMO1 gene (but not to genes that are not linked to ribosome biogenesis) and that the presence of Tor1p is associated with activation of gene activity. Persistent induction of DNA double-strand breaks or mTORC1 inhibition by rapamycin results in reduced levels of HMO1 mRNA, but only in the presence of Tor1p. This down-regulation is accompanied by eviction of Ifh1p and recruitment of Crf1p, followed by concerted dissociation of Hmo1p and Tor1p. These findings uncover a novel role for TOR kinase in control of gene activity by direct association with an RNA polymerase II–transcribed gene.

Control points in eucaryotic ribosome biogenesis

1991 ◽  
Vol 69 (1) ◽  
pp. 5-22 ◽  
Author(s):  
D. E. Larson ◽  
P. Zahradka ◽  
B. H. Sells
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Rna Polymerase Iii ◽  
Ribosomal Subunits ◽  
Rrna Species ◽  
Polymerase I ◽  
Ribosomal Precursor ◽  
Precursor Molecules

Ribosome biogenesis in eucaryotic cells involves the coordinated synthesis of four rRNA species, transcribed by RNA polymerase I (18S, 28S, 5.8S) and RNA polymerase III (5S), and approximately 80 ribosomal proteins translated from mRNAs synthesized by RNA polymerase II. Assembly of the ribosomal subunits in the nucleolus, the site of 45S rRNA precursor gene transcription, requires the movement of 5S rRNA and ribosomal proteins from the nucleoplasm and cytoplasm, respectively, to this structure. To integrate these events and ensure the balanced production of individual ribosomal components, different strategies have been developed by eucaryotic organisms in response to a variety of physiological changes. This review presents an overview of the mechanisms modulating the production of ribosomal precursor molecules and the rate of ribosome biogenesis in various biological systems.Key words: rRNA, ribosomal proteins, nucleolus, ribosome.

scholarly journals Assembly of Regulatory Factors on rRNA and Ribosomal Protein Genes in Saccharomyces cerevisiae

2007 ◽  
Vol 27 (19) ◽  
pp. 6686-6705 ◽  
Author(s):  
Koji Kasahara ◽  
Kazushige Ohtsuki ◽  
Sewon Ki ◽  
Kayo Aoyama ◽  
Hiroyuki Takahashi ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Ribosomal Proteins ◽  
High Mobility ◽  
Promoter Sequence ◽  
Rrna Gene ◽  
Dependent Manner ◽  
Ribosomal Protein Genes ◽  
Independent Manner

ABSTRACT HMO1 is a high-mobility group B protein that plays a role in transcription of genes encoding rRNA and ribosomal proteins (RPGs) in Saccharomyces cerevisiae. This study uses genome-wide chromatin immunoprecipitation to study the roles of HMO1, FHL1, and RAP1 in transcription of these genes as well as other RNA polymerase II-transcribed genes in yeast. The results show that HMO1 associates with the 35S rRNA gene in an RNA polymerase I-dependent manner and that RPG promoters (138 in total) can be classified into several distinct groups based on HMO1 abundance at the promoter and the HMO1 dependence of FHL1 and/or RAP1 binding to the promoter. FHL1, a key regulator of RPGs, binds to most of the HMO1-enriched and transcriptionally HMO1-dependent RPG promoters in an HMO1-dependent manner, whereas it binds to HMO1-limited RPG promoters in an HMO1-independent manner, irrespective of whether they are transcribed in an HMO1-dependent manner. Reporter gene assays indicate that these functional properties are determined by the promoter sequence.

scholarly journals Hog1 bypasses stress-mediated down-regulation of transcription by RNA polymerase II redistribution and chromatin remodeling

2012 ◽  
Vol 13 (11) ◽  
pp. R106 ◽  
Author(s):  
Mariona Nadal-Ribelles ◽  
Núria Conde ◽  
Oscar Flores ◽  
Juan González-Vallinas ◽  
Eduardo Eyras ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Chromatin Remodeling ◽  
Regulation Of Transcription ◽  
Down Regulation

scholarly journals Paired Box 9 (PAX9), the RNA polymerase II transcription factor, regulates human ribosome biogenesis and craniofacial development

PLoS Genetics ◽  
2020 ◽  
Vol 16 (8) ◽  
pp. e1008967
Author(s):  
Katherine I. Farley-Barnes ◽  
Engin Deniz ◽  
Maya M. Overton ◽  
Mustafa K. Khokha ◽  
Susan J. Baserga
Keyword(s):  
Transcription Factor ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Ribosome Biogenesis ◽  
Craniofacial Development ◽  
Rna Polymerase Ii Transcription

scholarly journals Loss of the Rpb4/Rpb7 Subcomplex in a Mutant Form of the Rpb6 Subunit Shared by RNA Polymerases I, II, and III

2003 ◽  
Vol 23 (9) ◽  
pp. 3329-3338 ◽  
Author(s):  
Qian Tan ◽  
Meredith H. Prysak ◽  
Nancy A. Woychik
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Rna Polymerases ◽  
Mutant Form ◽  
Direct Association ◽  
Before And After ◽  
Polymerase I ◽  
Conserved Core ◽  
Mutant Cells ◽  
Regulation Of Enzyme Activity

ABSTRACT We have identified a conditional mutation in the shared Rpb6 subunit, assembled in RNA polymerases I, II, and III, that illuminated a new role that is independent of its assembly function. RNA polymerase II and III activities were significantly reduced in mutant cells before and after the shift to nonpermissive temperature. In contrast, RNA polymerase I was marginally affected. Although the Rpb6 mutant strain contained two mutations (P75S and Q100R), the majority of growth and transcription defects originated from substitution of an amino acid nearly identical in all eukaryotic counterparts as well as bacterial ω subunits (Q100R). Purification of mutant RNA polymerase II revealed that two subunits, Rpb4 and Rpb7, are selectively lost in mutant cells. Rpb4 and Rpb7 are present at substoichiometric levels, form a dissociable subcomplex, are required for RNA polymerase II activity at high temperatures, and have been implicated in the regulation of enzyme activity. Interaction experiments support a direct association between the Rpb6 and Rpb4 subunits, indicating that Rpb6 is one point of contact between the Rpb4/Rpb7 subcomplex and RNA polymerase II. The association of Rpb4/Rpb7 with Rpb6 suggests that analogous subunits of each RNA polymerase impart class-specific functions through a conserved core subunit.

scholarly journals Alteration of nuclear lamin organization inhibits RNA polymerase II–dependent transcription

2002 ◽  
Vol 156 (4) ◽  
pp. 603-608 ◽  
Author(s):  
Timothy P. Spann ◽  
Anne E. Goldman ◽  
Chen Wang ◽  
Sui Huang ◽  
Robert D. Goldman
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Mammalian Cells ◽  
Protein A ◽  
Selective Inhibition ◽  
Chromatin Organization ◽  
Dominant Negative ◽  
Gene Activity ◽  
Structural Components ◽  
Nuclear Lamins

RTegulation of gene activity is mediated by alterations in chromatin organization. In addition, chromatin organization may be governed in part by interactions with structural components of the nucleus. The nuclear lamins comprise the lamina and a variety of nucleoplasmic assemblies that together are major structural components of the nucleus. Furthermore, lamins and lamin-associated proteins have been reported to bind chromatin. These observations suggest that the nuclear lamins may be involved in the regulation of gene activity. In this report, we test this possibility by disrupting the normal organization of nuclear lamins with a dominant negative lamin mutant lacking the NH2-terminal domain. We find that this disruption inhibits RNA polymerase II activity in both mammalian cells and transcriptionally active embryonic nuclei from Xenopus laevis. The inhibition appears to be specific for polymerase II as disruption of lamin organization does not detectably inhibit RNA polymerases I and III. Furthermore, immunofluorescence observations indicate that this selective inhibition of polymerase II–dependent transcription involves the TATA binding protein, a component of the basal transcription factor TFIID.

scholarly journals Nucleolar TFIIE plays a role in ribosomal biogenesis and performance

2020 ◽  
Author(s):  
Tamara Phan ◽  
Pallab Maity ◽  
Christina Ludwig ◽  
Lisa Streit ◽  
Jens Michaelis ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Ribosome Biogenesis ◽  
Initiation Site ◽  
Rna Polymerase I ◽  
Ribosomal Biogenesis ◽  
Protein Coding ◽  
Degenerative Disorder ◽  
And Performance ◽  
Polymerase I

Ribosome biogenesis is a highly energy-demanding process in eukaryotes which requires the concerted action of all three RNA polymerases. In RNA polymerase II transcription, the general transcription factor TFIIH is recruited by TFIIE to the initiation site of protein-coding genes. Distinct mutations in TFIIH and TFIIE give rise to the degenerative disorder trichothiodystrophy (TTD). Here we uncovered an unexpected role of TFIIE in ribosomal RNA synthesis by RNA polymerase I. With high resolution microscopy we detected TFIIE in the nucleolus where TFIIE binds to actively transcribed rDNA. Mutations in TFIIE affects gene-occupancy of RNA polymerase I, rRNA maturation, ribosomal assembly and performance. In consequence, the elevated translational error rate with imbalanced protein synthesis and turnover results in an increase in heat-sensitive proteins. Collectively, mutations in TFIIE - due to impaired ribosomal biogenesis and translational accuracy - lead to a loss of protein homeostasis (proteostasis) which can partly explain the clinical phenotype in TTD.

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