scholarly journals Structural mechanism of bivalent histone H3K4me3K9me3 recognition by the Spindlin1/C11orf84 complex in rRNA transcription activation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yongming Du ◽  
Yinxia Yan ◽  
Si Xie ◽  
Hao Huang ◽  
Xin Wang ◽  
...  
Keyword(s):  
Ribosomal Rna ◽  
Histone H3 ◽  
Transcription Activation ◽  
Rna Polymerase I ◽  
Structural Basis ◽  
Active Conformation ◽  
Structural Mechanism ◽  
Rrna Transcription ◽  
Polymerase I ◽  
Hp1 Proteins

AbstractSpindlin1 is a unique multivalent epigenetic reader that facilitates ribosomal RNA transcription. In this study, we provide molecular and structural basis by which Spindlin1 acts in complex with C11orf84 to preferentially recognize non-canonical bivalent mark of trimethylated lysine 4 and lysine 9 present on the same histone H3 tail (H3K4me3K9me3). We demonstrate that C11orf84 binding stabilizes Spindlin1 and enhances its association with bivalent H3K4me3K9me3 mark. The functional analysis suggests that Spindlin1/C11orf84 complex can displace HP1 proteins from H3K4me3K9me3-enriched rDNA loci, thereby facilitating the conversion of these poised rDNA repeats from the repressed state to the active conformation, and the consequent recruitment of RNA Polymerase I for rRNA transcription. Our study uncovers a previously unappreciated mechanism of bivalent H3K4me3K9me3 recognition by Spindlin1/C11orf84 complex required for activation of rRNA transcription.

scholarly journals SHPRH regulates rRNA transcription by recognizing the histone code in an mTOR-dependent manner

2017 ◽  
Vol 114 (17) ◽  
pp. E3424-E3433 ◽  
Author(s):  
Deokjae Lee ◽  
Jungeun An ◽  
Young-Un Park ◽  
Hungjiun Liaw ◽  
Roger Woodgate ◽  
...  
Keyword(s):  
Dna Repair ◽  
Actinomycin D ◽  
Mammalian Target Of Rapamycin ◽  
Histone H3 ◽  
Rna Polymerase I ◽  
Dependent Manner ◽  
Additional Function ◽  
Rrna Transcription ◽  
Plant Homeodomain ◽  
Polymerase I

Many DNA repair proteins have additional functions other than their roles in DNA repair. In addition to catalyzing PCNA polyubiquitylation in response to the stalling of DNA replication, SHPRH has the additional function of facilitating rRNA transcription by localizing to the ribosomal DNA (rDNA) promoter in the nucleoli. SHPRH was recruited to the rDNA promoter using its plant homeodomain (PHD), which interacts with histone H3 when the fourth lysine of H3 is not trimethylated. SHPRH enrichment at the rDNA promoter was inhibited by cell starvation, by treatment with actinomycin D or rapamycin, or by depletion of CHD4. SHPRH also physically interacted with the RNA polymerase I complex. Taken together, we provide evidence that SHPRH functions in rRNA transcription through its interaction with histone H3 in a mammalian target of rapamycin (mTOR)-dependent manner.

scholarly journals The Splicing ATPase Prp43p Is a Component of Multiple Preribosomal Particles

2005 ◽  
Vol 25 (21) ◽  
pp. 9269-9282 ◽  
Author(s):  
Simon Lebaron ◽  
Carine Froment ◽  
Micheline Fromont-Racine ◽  
Jean-Christophe Rain ◽  
Bernard Monsarrat ◽  
...  
Keyword(s):  
Affinity Purification ◽  
Rna Polymerase I ◽  
Rrna Processing ◽  
Rrna Transcription ◽  
Pol I ◽  
Final Maturation ◽  
Steady State Levels ◽  
Splicing Defects ◽  
Polymerase I ◽  
Two Hybrid

ABSTRACT Prp43p is a putative helicase of the DEAH family which is required for the release of the lariat intron from the spliceosome. Prp43p could also play a role in ribosome synthesis, since it accumulates in the nucleolus. Consistent with this hypothesis, we find that depletion of Prp43p leads to accumulation of 35S pre-rRNA and strongly reduces levels of all downstream pre-rRNA processing intermediates. As a result, the steady-state levels of mature rRNAs are greatly diminished following Prp43p depletion. We present data arguing that such effects are unlikely to be solely due to splicing defects. Moreover, we demonstrate by a combination of a comprehensive two-hybrid screen, tandem-affinity purification followed by mass spectrometry, and Northern analyses that Prp43p is associated with 90S, pre-60S, and pre-40S ribosomal particles. Prp43p seems preferentially associated with Pfa1p, a novel specific component of pre-40S ribosomal particles. In addition, Prp43p interacts with components of the RNA polymerase I (Pol I) transcription machinery and with mature 18S and 25S rRNAs. Hence, Prp43p might be delivered to nascent 90S ribosomal particles during pre-rRNA transcription and remain associated with preribosomal particles until their final maturation steps in the cytoplasm. Our data also suggest that the ATPase activity of Prp43p is required for early steps of pre-rRNA processing and normal accumulation of mature rRNAs.

scholarly journals Epigenetic Programming of the rRNA Promoter by MBD3

2007 ◽  
Vol 27 (13) ◽  
pp. 4938-4952 ◽  
Author(s):  
Shelley E. Brown ◽  
Moshe Szyf
Keyword(s):  
Small Interfering Rna ◽  
Rna Polymerase I ◽  
Rrna Genes ◽  
Rrna Gene ◽  
Rrna Transcription ◽  
Epigenetic Programming ◽  
Binding Factor ◽  
Upstream Binding Factor ◽  
Polymerase I ◽  
Interfering Rna

ABSTRACT Within the human genome there are hundreds of copies of the rRNA gene, but only a fraction of these genes are active. Silencing through epigenetics has been extensively studied; however, it is essential to understand how active rRNA genes are maintained. Here, we propose a role for the methyl-CpG binding domain protein MBD3 in epigenetically maintaining active rRNA promoters. We show that MBD3 is localized to the nucleolus, colocalizes with upstream binding factor, and binds to unmethylated rRNA promoters. Knockdown of MBD3 by small interfering RNA results in increased methylation of the rRNA promoter coupled with a decrease in RNA polymerase I binding and pre-rRNA transcription. Conversely, overexpression of MBD3 results in decreased methylation of the rRNA promoter. Additionally, overexpression of MBD3 induces demethylation of nonreplicating plasmids containing the rRNA promoter. We demonstrate that this demethylation occurs following the overexpression of MBD3 and its increased interaction with the methylated rRNA promoter. This is the first demonstration that MBD3 is involved in inducing and maintaining the demethylated state of a specific promoter.

scholarly journals BLM helicase facilitates RNA polymerase I-mediated ribosomal RNA transcription

2011 ◽  
Vol 21 (5) ◽  
pp. 1172-1183 ◽  
Author(s):  
Patrick M. Grierson ◽  
Kate Lillard ◽  
Gregory K. Behbehani ◽  
Kelly A. Combs ◽  
Saumitri Bhattacharyya ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Ribosomal Rna ◽  
Rna Polymerase I ◽  
Rna Transcription ◽  
Blm Helicase ◽  
Polymerase I

Events during eucaryotic rRNA transcription initiation and elongation: conversion from the closed to the open promoter complex requires nucleotide substrates

1988 ◽  
Vol 8 (5) ◽  
pp. 1940-1946
Author(s):  
E Bateman ◽  
M R Paule
Keyword(s):  
Rna Polymerase ◽  
Transcription Initiation ◽  
Topological Analysis ◽  
Acanthamoeba Castellanii ◽  
Rna Polymerase I ◽  
Initiation Factor ◽  
Rrna Transcription ◽  
Promoter Complex ◽  
Polymerase I

Chemical footprinting and topological analysis were carried out on the Acanthamoeba castellanii rRNA transcription initiation factor (TIF) and RNA polymerase I complexes with DNA during transcription initiation and elongation. The results show that the binding of TIF and polymerase to the promoter does not alter the supercoiling of the DNA template and the template does not become sensitive to modification by diethylpyrocarbonate, which can identify melted DNA regions. Thus, in contrast to bacterial RNA polymerase, the eucaryotic RNA polymerase I-promoter complex is in a closed configuration preceding addition of nucleotides in vitro. Initiation and 3'-O-methyl CTP-limited translocation by RNA polymerase I results in separation of the polymerase-TIF footprints, leaving the TIF footprint unaltered. In contrast, initiation and translocation result in a significant change in the conformation of the polymerase-DNA complex, culminating in an unwound DNA region of at least 10 base pairs.

scholarly journals Structural basis for virulence regulation in Vibrio cholerae by unsaturated fatty acid components of bile

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Justin T. Cruite ◽  
Gabriela Kovacikova ◽  
Kenzie A. Clark ◽  
Anne K. Woodbrey ◽  
Karen Skorupski ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Structural Model ◽  
Unsaturated Fatty Acids ◽  
Diarrheal Disease ◽  
Bacterial Pathogen ◽  
Virulence Gene ◽  
Structural Basis ◽  
Active Conformation ◽  
Structural Mechanism ◽  
Virulence Gene Regulation

AbstractThe AraC/XylS-family transcriptional regulator ToxT is the master virulence activator of Vibrio cholerae, the gram-negative bacterial pathogen that causes the diarrheal disease cholera. Unsaturated fatty acids (UFAs) found in bile inhibit the activity of ToxT. Crystal structures of inhibited ToxT bound to UFA or synthetic inhibitors have been reported, but no structure of ToxT in an active conformation had been determined. Here we present the 2.5 Å structure of ToxT without an inhibitor. The structure suggests release of UFA or inhibitor leads to an increase in flexibility, allowing ToxT to adopt an active conformation that is able to dimerize and bind DNA. Small-angle X-ray scattering was used to validate a structural model of an open ToxT dimer bound to the cholera toxin promoter. The results presented here provide a detailed structural mechanism for virulence gene regulation in V. cholerae by the UFA components of bile and other synthetic ToxT inhibitors.

scholarly journals In vitroevidence that eukaryotic ribosomal RNA transcription is regulated by modification of RNA polymerase I

1984 ◽  
Vol 12 (21) ◽  
pp. 8161-8180 ◽  
Author(s):  
Marvin R. Paule ◽  
Calvin T. Iida ◽  
Peter J. Perna ◽  
Guy H. Harris ◽  
Deborah A. Knoll ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Ribosomal Rna ◽  
Rna Polymerase I ◽  
Rna Transcription ◽  
Polymerase I
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