Factors Responsible for Modulation of Ribosomal RNA Transcription (original) (raw)
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Molecular and Cellular Biology, 1986
We have studied the protein components and nucleic acid sequences involved in stably activating the ribosomal DNA (rDNA) template and in directing accurate transcription of mammalian rRNA genes. Two protein components are necessary to catalyze rDNA transcription, and these have been extensively purified. The first, factor D, can stably associate by itself with the rDNA promoter region and is responsible for template commitment. The second component, factor C, which appears to be an activated subset of polymerase I, can stably bind to the factor D-rDNA complex but not to the rDNA in the absence of factor D. A third component which had been previously identified as a rDNA transcription factor is shown to be a RNase inhibitor. Extending our earlier observation that the approximately 150-base-pair mouse rDNA promoter consists of a minimal essential region (residues approximately -35 to approximately +9) and additional upstream stimulatory domains, we now report that each of these promot...
The nucleotide sequence of the initiation region of the ribosomal transcription unit from mouse
Nucleic Acids Research, 1981
The 5' end of 45S pre-rRNA has been located on a cloned rDNA fragment from mouse by r-loop mapping and the nuclease S1 protection technique. 45S pre-rRNA could be shown to represent the primary transcript of the ribosomal genes because 5' polyphosphate termini have been detected by an enzymatic assay. The sequence of about 1100 nucleotides surrounding the initiation site for ribosomal RNA transcription has been determined. Features of this region of the ribosomal DNA will be discussed. A comparison of the nucleotide sequence with corresponding areas of ribosomal genes from other eukaryotes does not reveal significant homology in the region of transcription initiation.
Transcription initiation site of rat ribosomal DNA
Nucleic Acids Research, 1982
The sequence of 1,100 nucleotides surrounding the transcription initiation site of a cloned rat ribosomal RNA gene (rDNA) has been determined. The location of the 5' terminus of 45S pre-rRNA was determined by S1 nuclease mapping, reverse transcriptase elongation and confirmed by in vitro capping of 45S rRNA and in vitro transcription. Two different plasmid subclones, from two separate genomic clones of rat rDNA, contained the identical sequence surrounding the transcription initiation site:-°GGAGATATAT 1GCTGACACGC TGTCCTTTTG+20. Relatively long, greater than 15 base pairs, regions of sequence homology were found when the sequences of the initiation regions of rat and mouse rDNA
The Journal of Cell Biology, 2000
Nuclear RNA transcription is repressed when eukaryotic cells enter mitosis. Here, we found that the derepression of ribosomal gene (rDNA) transcription that normally takes place in telophase may be induced in prometaphase, metaphase, and anaphase mitotic HeLa cells, and therefore appears not to be dependent on completion of mitosis. We demonstrate for the first time that in vivo inhibition of the cdc2cyclin B kinase activity is sufficient to give rise to okadaic acid-sensitive dephosphorylation of the mitotically phosphorylated forms of components of the rDNA transcription machinery, and consequently to restore rDNA transcription in mitotic cells. These results, showing that during mitosis the rDNA transcription machinery is maintained repressed by the cdc2-cyclin B kinase activity, provide an in vivo demonstration of the cell cycle-dependent regulation of rDNA transcription.
Transcriptional Elements Involved in the Repression of Ribosomal Protein Synthesis
Molecular and Cellular Biology, 1999
The ribosomal proteins (RPs) of Saccharomyces cerevisiae are encoded by 137 genes that are among the most transcriptionally active in the genome. These genes are coordinately regulated: a shift up in temperature leads to a rapid, but temporary, decline in RP mRNA levels. A defect in any part of the secretory pathway leads to greatly reduced ribosome synthesis, including the rapid loss of RP mRNA. Here we demonstrate that the loss of RP mRNA is due to the rapid transcriptional silencing of the RP genes, coupled to the naturally short lifetime of their transcripts. The data suggest further that a global inhibition of polymerase II transcription leads to overestimates of the stability of individual mRNAs. The transcription of most RP genes is activated by two Rap1p binding sites, 250 to 400 bp upstream from the initiation of transcription. Rap1p is both an activator and a silencer of transcription. The swapping of promoters between RPL30 and ACT1 or GAL1 demonstrated that the Rap1p binding sites of RPL30 are sufficient to silence the transcription of ACT1 in response to a defect in the secretory pathway. Sir3p and Sir4p, implicated in the Rap1p-mediated repression of silent mating type genes and of telomere-proximal genes, do not influence such silencing of RP genes. Sir2p, implicated in the silencing both of the silent mating type genes and of genes within the ribosomal DNA locus, does not influence the repression of either RP or rRNA genes. Surprisingly, the 180-bp sequence of RPL30 that lies between the Rap1p sites and the transcription initiation site is also sufficient to silence the Gal4p-driven transcription in response to a defect in the secretory pathway, by a mechanism that requires the silencing region of Rap1p. We conclude that for Rap1p to activate the transcription of an RP gene it must bind to upstream sequences; yet for Rap1p to repress the transcription of an RP gene it need not bind to the gene directly. Thus, the cell has evolved a two-pronged approach to effect the rapid extinction of RP synthesis in response to the stress imposed by a heat shock or by a failure of the secretory pathway. Calculations based on recent transcriptome data and on the half-life of the RP mRNAs suggest that in a rapidly growing cell the transcription of RP mRNAs accounts for nearly 50% of the total transcriptional events initiated by RNA polymerase II. Thus, the sudden silencing of the RP genes must have a dramatic effect on the overall transcriptional economy of the cell.
The Epigenetics of rRNA Genes: From Molecular to Chromosome Biology
Annual Review of Cell and Developmental Biology, 2008
In eukaryotes, the genes encoding ribosomal RNAs (rDNA) exist in two distinct epigenetic states that can be distinguished by a specific chromatin structure that is maintained throughout the cell cycle and is inherited from one cell to another. The fact that even in proliferating cells with a high demand of protein synthesis a fraction of rDNA is silenced provides a unique possibility to decipher the mechanism underlying epigenetic regulation of rDNA. This chapter summarizes our knowledge of the molecular mechanisms that establish and propagate the epigenetic state of rRNA genes, unraveling a complex interplay of DNA methyltransferases and histone-modifying enzymes that act in concert with chromatin remodeling complexes and RNA-guided mechanisms to define the transcriptional state of rDNA. We also review the critical role of the RNA polymerase I transcription factor UBF in the formation of active nucleolar organizer regions (NORs) and maintenance of the euchromatic state of rRNA genes.