RNA-polymerase-I-directed rDNA transcription, life and works

Russell, Jackie; Zomerdijk, Joost C.B.M.

doi:10.1016/j.tibs.2004.12.008

Cited by 251 publications

(222 citation statements)

References 86 publications

(128 reference statements)

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“…Consistent with the less rRNA and protein (39,40), DEDD Ϫ/Ϫ cells were smaller in size than DEDD ϩ/ϩ cells by FACS analysis (a 20-25% reduction in the average size in both forward-and side-scatter parameters; Fig. 4A).…”

Section: Lack Of Dedd Did Not Influence Rrna Synthesis Rates During Tsupporting

confidence: 61%

Death-effector domain-containing protein DEDD is an inhibitor of mitotic Cdk1/cyclin B1

Arai

Miyake

Voit

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Accumulating evidence has shown that many molecules, including some cyclin-dependent kinases (Cdks) and cyclins, as well as the death-effector domain (DED)-containing FADD, function for both apoptosis and cell cycle. Here we identified that DEDD, which also possesses the DED domain, acts as a novel inhibitor of the mitotic Cdk1/cyclin B1 complex. DEDD associates with mitotic Cdk1/cyclin B1 complexes via direct binding to cyclin B1 and reduces their function. In agreement, kinase activity of nuclear Cdk1/cyclin B1 in DEDD-null (DEDD ؊/؊ ) embryonic fibroblasts is increased compared with that in DEDD ؉/؉ cells, which results in accelerated mitotic progression, thus exhibiting a shortened G2/M stage. Interestingly, DEDD ؊/؊ cells also demonstrated decreased G1 duration, which perhaps enhanced the overall reduction in rRNA amounts and cell volume, primarily caused by the rapid termination of rRNA synthesis before cell division. Likewise, DEDD ؊/؊ mice show decreased body and organ weights relative to DEDD ؉/؉ mice. Thus, DEDD is an impeder of cell mitosis, and its absence critically influences cell and body size via modulation of rRNA synthesis.apoptosis ͉ cell cycle ͉ cell size ͉ cyclin-dependent kinase ͉ mitosis C ell size control is tightly associated with cell cycle regulation.The consensus is that cells predominantly increase their volume during the G 1 cell cycle phase (1-3). However, evidence has demonstrated that a proper cell growth also undergoes before cell division (4, 5), where rRNA and protein synthesis achieve maximal activity. The duration of this period is defined by the activation of cyclin-dependent kinase 1 (Cdk1)/cyclin B1 complexes, which is proceeded through dephosphorylation of the inhibitory residues of Cdk1 and Tyr-15, and also Thr-14 in higher eukaryotes, by the Cdc25 phosphatase family (4-10), followed by translocation of Cdk1/cyclin B1 into the nucleus. Thus, defects in Cdc25 genes delay mitotic entry, resulting in increased cell size (11-13). In contrast, an inadequate duration before division, due to aberrant phosphorylation of Tyr-15, causes cells to enter mitosis before sufficient growth, resulting in decreased size of the daughter cells (14-17). Interestingly, the loss of Wee1-related kinases, responsible for phosphorylation of Thr-14/Tyr-15, causes premature cell division in yeast, Xenopus, or Drosophila cells, but not in higher mammalian cells (4,5,9,10,(15)(16)(17)(18). This suggests the presence of alternative mechanism(s), which may also influence cell size, particularly in mammalian cells. However, the responsible mechanisms have remained unclear.Linkage of cell cycle and apoptosis has been recognized for many molecules, including some Cdks and cyclins (19,20). Recently, it was also demonstrated that the death-effector domain (DED)-containing molecule FADD regulates mitosis (21). The DED domain of Ϸ80 amino acid residues is well conserved in various death-inducing proteins (22-24). The DED of FADD recruits two DED-containing caspases, caspase-8 and caspase-10, to form the deat...

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Section: Lack Of Dedd Did Not Influence Rrna Synthesis Rates During Tsupporting

confidence: 61%

Death-effector domain-containing protein DEDD is an inhibitor of mitotic Cdk1/cyclin B1

Arai

Miyake

Voit

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Ribosomal RNA gene transcription is tightly regulated in order to provide the proper amount of rRNA for ribosome assembly, according to the cellular need for protein synthesis [48][49][50]. Available evidence indicates that eukaryotes have more rRNA genes than are required for ribosome biogenesis under most physiological conditions such that they regulate the effective dosage of the rRNA genes they possess [51].…”

Section: Rrna Gene Dosage Control Mechanisms and The Mammalian Norc Cmentioning

confidence: 99%

rRNA gene silencing and nucleolar dominance: Insights into a chromosome-scale epigenetic on/off switch

Preuss

Pikaard

2007

Biochimica et Biophysica Acta (BBA) - Gene Structure and Expres

135

105

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Ribosomal RNA (rRNA) gene transcription accounts for most of the RNA in prokaryotic and eukaryotic cells. In eukaryotes, there are hundreds (to thousands) of rRNA genes tandemly repeated head-to-tail within nucleolus organizer regions (NORs) that span millions of basepairs. These nucleolar rRNA genes are transcribed by RNA Polymerase I (Pol I) and their expression is regulated according to the physiological need for ribosomes. Regulation occurs at several levels, one of which is an epigenetic on/off switch that controls the number of active rRNA genes. Additional mechanisms then fine-tune transcription initiation and elongation rates to dictate the total amount of rRNA produced per gene. In this review, we focus on the DNA and histone modifications that comprise the epigenetic on/off switch. In both plants and animals, this system is important for controlling the dosage of active rRNA genes. The dosage control system is also responsible for the chromatinmediated silencing of one parental set of rRNA genes in genetic hybrids, a large-scale epigenetic phenomenon known as nucleolar dominance.Keywords epigenetic phenomena; RNA polymerase I; DNA methylation; cytosine methylation; histone methylation; histone deacetylation; histone deacetylase; transcription; ribosomal RNA; nucleolus; nucleolus organizer region Large scale cytological effects of rRNA gene regulation: nucleolus and secondary constriction formationThe most prominent feature of a eukaryotic nucleus during interphase is the nucleolus (Figure 1), a region that contains relatively little chromosomal DNA but is rich in RNAs, proteins and ribonucleoprotein particles, including the large and small ribosome subunits as they undergo assembly [1][2][3]. The location of a nucleolus is not determined randomly; instead its formation is determined by the position of a discrete chromosomal locus known as a nucleolus organizer region, or NOR [4]. This fact was discovered based on an intriguing property: upon condensation of chromosomes at metaphase, NORs fail to condense to the same extent as surrounding chromosomal sequences and thus give rise to "secondary constrictions", with "primary constrictions" being defined as the centromeres (see Figure 1). Heitz initially noted that nucleoli form at, or very near, the sites of secondary constrictions [5] and McClintock soon thereafter obtained direct evidence [6]. She identified a maize line in which a chromosome break at or near the secondary constriction on chromosome 9, followed by translocation of one *Author to whom correspondence should be addressed: pikaard@biology2.wustl.edu, phone: Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the conte...

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“…Previous studies have identified essential components of the Pol I transcription apparatus as well as important cis-elements in Pol I promoters and revealed some potential mechanisms for regulation of transcription initiation (for reviews, see refs. [1][2][3][4][5]. Unlike Pol II, however, little is known regarding mechanisms that regulate postinitiation steps of transcription by Pol I.…”

mentioning

confidence: 99%

RNA polymerase II elongation factors Spt4p and Spt5p play roles in transcription elongation by RNA polymerase I and rRNA processing

Schneider

French

Osheim

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

103

143

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Previous investigations into the mechanisms that control RNA Polymerase (Pol) I transcription have primarily focused on the process of transcription initiation, thus little is known regarding postinitiation steps in the transcription cycle. Spt4p and Spt5p are conserved throughout eukaryotes, and they affect elongation by Pol II. We have found that these two proteins copurify with Pol I and associate with the rDNA in vivo. Disruption of the gene for Spt4p resulted in a modest decrease in growth and rRNA synthesis rates at the permissive temperature, 30°C. Furthermore, biochemical and EM analyses showed clear defects in rRNA processing. These data suggest that Spt4p, Spt5p, and, potentially, other regulators of Pol I transcription elongation play important roles in coupling rRNA transcription to its processing and ribosome assembly.yeast Saccharomyces cerevisiae T he synthesis of ribosomal RNA (rRNA) by RNA Polymerase (Pol) I is an important step in the synthesis of ribosomes, and its regulation is closely linked to the nutrient conditions and growth potential for the cell. Previous studies have identified essential components of the Pol I transcription apparatus as well as important cis-elements in Pol I promoters and revealed some potential mechanisms for regulation of transcription initiation (for reviews, see refs. 1-5). Unlike Pol II, however, little is known regarding mechanisms that regulate postinitiation steps of transcription by Pol I.One well characterized Pol II transcription elongation factor in yeast is a complex of two proteins, Spt4p and Spt5p (the complex will be referred to as Spt4͞5 here). The SPT4 and SPT5 genes were among many genes isolated for their ability to suppress transcription defects caused by insertions of the retrotransposon Ty1 (or the Ty1 long terminal repeats, ␦) in the 5Ј noncoding regions of yeast genes (6). Swanson and Winston (7) later showed that Spt4͞5 associates with Spt6p, which affects Pol II elongation through chromatin. However, Spt4p and Spt5p also form a separate complex, devoid of Spt6p, that associates with Pol II physically and genetically, and this interaction is important for transcription elongation (8). More recent work has shown that deletion of the nonessential gene SPT4 results in reduced efficiency of Pol II elongation through GC-rich DNA sequences (9) and a general decrease in Pol II processivity (10). Taken together, all of these data clearly support a role for Spt4͞5 in transcription elongation by Pol II in yeast.Spt4͞5 also plays a role in Pol II transcription elongation in mammalian cells. The mammalian homologues of Spt4p and Spt5p form a complex called the 5,6-dichloro-1-␤-Dribofuranosylbenzimidazole (DRB) sensitivity-inducing factor (DSIF), which was originally identified as a factor that induces a DRB-dependent arrest of elongating Pol II complexes in reconstituted in vitro transcription assays (11). It was demonstrated that under nucleotide-limiting conditions, DSIF could also increase the rate of elongation of Pol II in vitro. Thus, work in mam...

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RNA-polymerase-I-directed rDNA transcription, life and works

Cited by 251 publications

References 86 publications

Death-effector domain-containing protein DEDD is an inhibitor of mitotic Cdk1/cyclin B1

Death-effector domain-containing protein DEDD is an inhibitor of mitotic Cdk1/cyclin B1

rRNA gene silencing and nucleolar dominance: Insights into a chromosome-scale epigenetic on/off switch

RNA polymerase II elongation factors Spt4p and Spt5p play roles in transcription elongation by RNA polymerase I and rRNA processing

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