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At least 289 records · Page 16Linked to original sources
PubMed1998

Temporal regulation of RNA polymerase II by Srb10 and Kin28 cyclin-dependent kinases.

Two cyclin-dependent kinases have been identified in yeast and mammalian RNA polymerase II transcription initiation complexes. We find that the two yeast kinases are indistinguishable in their ability to phosphorylate the RNA polymerase II CTD, and yet in living cells one kinase is a positive regulator and the other a negative regulator. This paradox is resolved by the observation that the negative regulator, Srb10, is uniquely capable of phosphorylating the CTD prior to formation of the initiation complex on promoter DNA, with consequent inhibition of transcription. In contrast, the TFIIH kinase phosphorylates the CTD only after the transcription apparatus is associated with promoter DNA. These results reveal that the timing of CTD phosphorylation can account for the positive and negative functions of the two kinases and provide a model for Srb10-dependent repression of genes involved in cell type specificity, meiosis, and sugar utilization.

Cell Cycle↗
PubMed1984

Effects of antiestrogens on the estrogen-regulated pS2 RNA and the 52- and 160-kilodalton proteins in MCF7 cells and two tamoxifen-resistant sublines.

The effects of estradiol and antiestrogens on two estrogen-regulated proteins (52 and 160 kDa) and an estrogen-inducible mRNA (pS2) have been measured in the MCF7 human breast cancer cell line and two tamoxifen-resistant sublines. In MCF7 cells, tamoxifen (or nafoxidine) alone does not significantly affect pS2 mRNA levels nor transcription of the pS2 gene but completely antagonizes the ability of estradiol to increase pS2 RNA levels. The estrogen-mediated increase in pS2 mRNA levels resembles that of two estrogen-regulated proteins (52 and 160 kDa) that are released from MCF7 cells into the culture medium. This is distinct from the estrogen-mediated increase in progesterone receptor which is also obtained by tamoxifen treatment. In the two tamoxifen-resistant sublines (R27 and RTx6), tamoxifen does not increase pS2 mRNA levels or 160-kDa protein production but increases the production of the 52-kDa protein. These results show that in these tamoxifen-resistant cells, tamoxifen has become fully estrogenic for one, but not all estrogen-regulated responses.

Breast Neoplasms↗
PubMed1999

Regulation of RNA polymerase I transcription in response to F9 embryonal carcinoma stem cell differentiation.

Dramatic changes in the patterns of transcription are a common feature of early development. We have used F9 embryonal carcinoma cells as a model system to study gene regulation during an early stage of murine embryogenesis. We find that transcription by RNA polymerase I decreases when F9 cells differentiate into parietal endoderm. The reduced rate of transcription is associated with a down-regulation of several components of the class I transcription apparatus. The most substantial change involves the essential factor SL1, which is a multisubunit complex that contains the TATA-binding protein and three TATA-binding protein-associated factors (TAFs). The abundance of two of these TAFs, TAFI48 and TAFI95, decreases during F9 cell differentiation. Developmental regulation of a specific class of genes may therefore be achieved through changes in the availability of TAFs.

Animals↗
PubMed2001

Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing.

RNAi is a gene-silencing phenomenon triggered by double-stranded (ds) RNA and involves the generation of 21 to 26 nt RNA segments that guide mRNA destruction. In Caenorhabditis elegans, lin-4 and let-7 encode small temporal RNAs (stRNAs) of 22 nt that regulate stage-specific development. Here we show that inactivation of genes related to RNAi pathway genes, a homolog of Drosophila Dicer (dcr-1), and two homologs of rde-1 (alg-1 and alg-2), cause heterochronic phenotypes similar to lin-4 and let-7 mutations. Further we show that dcr-1, alg-1, and alg-2 are necessary for the maturation and activity of the lin-4 and let-7 stRNAs. Our findings suggest that a common processing machinery generates guide RNAs that mediate both RNAi and endogenous gene regulation.

Animals↗
PubMed2004

Regulation of RNA polymerase through the secondary channel.

High-resolution crystal structures have highlighted functionally important regions in multisubunit RNA polymerases, including the secondary channel, or pore, which is postulated to allow the diffusion of small molecules both into and out of the active center of the enzyme. Recent work from several groups has illustrated how regulatory factors and small molecules can exploit the secondary channel to gain access to the active site and modify the transcription properties of RNA polymerase.

Catalytic Domain↗
PubMed1996

Regulation of RNA polymerase sigma subunit synthesis in Escherichia coli: intracellular levels of four species of sigma subunit under various growth conditions.

By a quantitative Western immunoblot analysis, the intracellular levels of two principal sigma subunits, sigma 70 (sigma D, the rpoD gene product) and sigma 38 (sigma S, the rpoS gene product), and of two minor sigma subunits, sigma 54 (sigma N, the rpoN gene product) and sigma 28 (sigma F, the rpoF gene product), were determined in two Escherichia coli strains, W3110 and MC4100. The results indicated that the levels of sigma 54 and sigma 28 are maintained at 10 and 50%, respectively, of the level of sigma 70 in both strains growing at both exponential and stationary phases, but in agreement with the previous measurement for strain MC4100 (M. Jishage and A. Ishihama, J. Bacteriol. 177:6832-6835, 1995), the level of sigma 38 was undetectable at the exponential growth phase but increased at 30% of the level of sigma 70 at the stationary phase. Stress-coupled change in the intracellular level was observed for two sigma subunits: (i) the increase in sigma 38 level and the decrease in sigma 28 level upon exposure to heat shock at the exponential phase and (ii) the increase in sigma 38 level under high-osmolality conditions at both the exponential and stationary phases.

Bacterial Proteins↗
PubMed1973

Regulation of RNA synthesis in fibroblasts during transition from resting to growing state.

Addition of serum, containing fibroblast growth factors, to a culture of resting 3T6 cells stimulates a transition to the growing state. Studies of ghost monolayers prepared with the aid of detergent at intervals after stimulation showed an increase in the rate of ribosomal RNA synthesis within 10 min. The rate continued to increase for many hours and reached a level 2.5- to 3.5-fold higher by the time DNA synthesis began. The increasing rate of ribosomal RNA synthesis appeared independent of an increase in the number of ribosomal genes, since it was not affected by prevention of DNA synthesis with cytosine arabinoside. In contrast to ribosomal RNA, the overall rate of transscription of heterogeneous nuclear RNA was not directly affected by serum growth factors and does not appear to be regulated during the transition from resting to growing state. It seems, instead, to be fixed in relation to the amount of template, for it increases proportionally to DNA content.

Basidiomycota↗
PubMed2004

Regulation of RNA function by aminoacylation and editing?

The chemical modification of nucleic acids is a ubiquitous phenomenon. Aminoacylation of tRNAs by aminoacyl-tRNA synthetases (ARSs) is a reaction essentially devoted to protein synthesis but it is used also as an emergency mechanism to recycle stalled ribosomes, and it is required for genome replication in some RNA viruses. In several aminoacyl-tRNA synthetases a correction mechanism known as editing is present to prevent aminoacylation errors. Genome data reveal a growing number of open reading frames encoding ARS-like proteins. This strongly suggests the existence of a widespread and nonconventional machinery for aminoacylation and editing. Here we review the different biological functions of aminoacylation and editing; also we propose an evolutionary scenario for the origin of these two reactions, and hypothesize an extant role for RNA charging and editing outside the genetic code.

Amino Acyl-tRNA Synthetases↗
PubMed2003

Phosphorylation of rubella virus capsid regulates its RNA binding activity and virus replication.

Rubella virus is an enveloped positive-strand RNA virus of the family TOGAVIRIDAE: Virions are composed of three structural proteins: a capsid and two membrane-spanning glycoproteins, E2 and E1. During virus assembly, the capsid interacts with genomic RNA to form nucleocapsids. In the present study, we have investigated the role of capsid phosphorylation in virus replication. We have identified a single serine residue within the RNA binding region that is required for normal phosphorylation of this protein. The importance of capsid phosphorylation in virus replication was demonstrated by the fact that recombinant viruses encoding hypophosphorylated capsids replicated at much lower titers and were less cytopathic than wild-type virus. Nonphosphorylated mutant capsid proteins exhibited higher affinities for viral RNA than wild-type phosphorylated capsids. Capsid protein isolated from wild-type strain virions bound viral RNA more efficiently than cell-associated capsid. However, the RNA-binding activity of cell-associated capsids increased dramatically after treatment with phosphatase, suggesting that the capsid is dephosphorylated during virus assembly. In vitro assays indicate that the capsid may be a substrate for protein phosphatase 1A. As capsid is heavily phosphorylated under conditions where virus assembly does not occur, we propose that phosphorylation serves to negatively regulate binding of viral genomic RNA. This may delay the initiation of nucleocapsid assembly until sufficient amounts of virus glycoproteins accumulate at the budding site and/or prevent nonspecific binding to cellular RNA when levels of genomic RNA are low. It follows that at a late stage in replication, the capsid may undergo dephosphorylation before nucleocapsid assembly occurs.

Amino Acid Sequence↗
PubMed2002

Ebola virus VP30-mediated transcription is regulated by RNA secondary structure formation.

The nucleocapsid protein VP30 of Ebola virus (EBOV), a member of the Filovirus family, is known to act as a transcription activator. By using a reconstituted minigenome system, the role of VP30 during transcription was investigated. We could show that VP30-mediated transcription activation is dependent on formation of a stem-loop structure at the first gene start site. Destruction of this secondary structure led to VP30-independent transcription. Analysis of the transcription products of bicistronic minigenomes with and without the ability to form the secondary structure at the first transcription start signal revealed that transcription initiation at the first gene start site is a prerequisite for transcription of the second gene, independent of the presence of VP30. When the transcription start signal of the second gene was exchanged with the transcription start signal of the first gene, transcription of the second gene also was regulated by VP30, indicating that the stem-loop structure of the first transcription start site acts autonomously and independently of its localization on the RNA genome. Our results suggest that VP30 regulates a very early step of EBOV transcription, most likely by inhibiting pausing of the transcription complex at the RNA structure of the first transcription start site.

Animals↗
PubMed2001

A viral double-stranded RNA up regulates the fungal virulence of Nectria radicicola.

Double-stranded RNAs (dsRNAs) are widespread in plant pathogenic fungi, but their functions in fungal hosts remain mostly unclear, with a few exceptions. We analyzed dsRNAs from Nectria radicicola, the causal fungus of ginseng root rot. Four distinct sizes of dsRNAs, 6.0, 5.0, 2.5, and 1.5 kbp, were detected in 24 out of the 81 strains tested. Curing tests of individual dsRNAs suggested that the presence of 6.0-kbp dsRNA was associated with high levels of virulence, sporulation, laccase activity, and pigmentation in this fungus. The 6.0-kbp dsRNA-cured strains completely lost virulence-related phenotypes. This 6.0-kbp dsRNA was reintroduced by hyphal anastomosis to a dsRNA-cured strain marked with hygromycin resistance, which resulted in the restoration of virulence-related phenotypes. These results strongly suggest that 6.0-kbp dsRNA up regulates fungal virulence in N. radicicola. Sequencing of several cDNA clones derived from 6.0-kbp dsRNA revealed the presence of a RNA-dependent RNA polymerase (RDRP) gene. Phylogenetic analysis showed that this gene is closely related to those of plant cryptic viruses. Biochemical analyses suggested that the 6.0-kbp dsRNA may regulate fungal virulence through signal-transduction pathways involving cyclic AMP-dependent protein kinase and protein kinase C.

Amino Acid Sequence↗
PubMed1996

Evidence of post-transcriptional regulation of U6 small nuclear RNA.

Mechanisms regulating the intracellular level of endogenous U6 small nuclear RNA were studied by transient transfection of ectopic U6 gene constructs into immortalized normal and malignant human cell lines. Transfection and expression of a modified U6 gene containing native promoter, capping, and termination sequences but lacking all highly conserved internal spliceosome sequences produced dose-dependent effects on endogenous U6 gene expression. At low transfection doses, no significant changes in endogenous U6 RNA levels or half-life were noted. However, as the dose of the transfected gene and its expression increased, native U6 RNA levels dramatically decreased in association with an apparent decrease in U6 RNA half-life. Down-regulation of native U6 RNA levels was transient, with recovery noted within 48-96 h in conjunction with declining expression of the ectopic gene. These modulatory effects appeared specific to endogenous U6 transcripts, because no changes were noted in 7sk, U1, U3, or 5S RNA levels or half-lives. Transfection with an unmodified U6 gene did not alter total U6 transcript levels but did produce a similar dose-dependent decrease in U6 RNA half-life. These studies suggest a hitherto unrecognized U6-specific intracellular regulatory mechanism, through which over-accumulation of U6 small nuclear RNA is prevented.

Cell Line↗
PubMed1994

RNA splicing regulates the activity of a SH2 domain-containing protein tyrosine phosphatase.

A cDNA which encodes a protein tyrosine phosphatase with two src homology 2 (SH2) domains was isolated from a rat brain cDNA library. This phosphatase appears to be a rat homologue of PTP1D based on its amino acid sequence. The gene is expressed in a variety of tissues, and its mRNA is enriched in the brain, skeletal muscle, and lung. An RNA splice variant (PTP1Di) was also isolated which has four additional amino acid residues (Ala-Leu-Leu-Gln) in the catalytic domain. The catalytic domains of PTP1D and PTP1Di were expressed in Escherichia coli as glutathione S-transferase fusion proteins and purified to near homogeneity. Whereas both PTP1D and PTP1Di had catalytic activity, the Vmax of PTP1Di relative to that of PTP1D was 8-fold lower for para-nitrophenylphosphate, 20-fold lower for nicotinic acetylcholine receptor, and 14-fold lower for myelin basic protein. The Km values of PTP1Di were lower than those of PTP1D for both nicotinic acetylcholine receptor and myelin basic protein, suggesting a higher affinity of PTP1Di for a protein substrate. These two forms also differed in optimum pH for para-nitrophenylphosphate and sensitivity to the inhibitory effects of vanadate, molybdate, and spermidine. In order to see if this insert would affect the catalytic activity of other related phosphatases, the 4-amino acids were inserted in the corresponding region of the catalytic domain of PTP1C. Whereas both the wild type and PTP1Ci which contained the 4-amino acid insert dephosphorylated para-nitrophenylphosphate, nicotinic receptor, and myelin basic protein, the enzyme activity of PTP1Ci was only 11-24% of that of PTP1C wild type. These results demonstrate that the 4-amino acid insert in the catalytic domains of PTP1D down-regulates its phosphatase activity and suggests that RNA splicing may serve as a regulatory mechanism of protein tyrosine phosphatase activity.

Amino Acid Sequence↗
PubMed1987

Hormonal regulation of RNA synthesis and specific gene expression in Xenopus oviduct cells in primary culture.

The studies described in this report were carried out as a first step towards the elucidation of mechanisms underlying the tissue specificity of regulation of gene expression by estrogen. Using a procedure established earlier in our laboratory for primary culture of Xenopus hepatocytes, we have characterized how estradiol-17 beta and progesterone affect the rate of synthesis of total RNA and that of accumulation of two oviduct-specific mRNAs in Xenopus oviduct cells in primary culture. In cells that had recovered from 'culture shock' 3 days after they were plated out, both hormones had only a slight or no effect on the overall rate of labelling of newly synthesized RNA over 24 h. Cloned cDNA probes for two mRNAs, termed 7F and 6G and specifying as yet unknown proteins expressed in the oviduct and not in the liver, were used to quantify the two mRNAs. The levels of both mRNAs declined for the first 2 days in culture after which they were stabilized. When added to the oviduct cell cultures 3 days after they were plated out, estradiol increased the steady-state concentration (relative to total RNA) of 7F and 6G mRNAs by 3- to 7-fold after 60-80 h, but with different time-course and dose-response kinetics for the two messages. The antiestrogen tamoxifen also exerted different degrees of antagonist effect on the estrogen-induced accumulation of 7F and 6G mRNAs. Although the protein products of these two oviduct-specific mRNAs have not yet been characterized, these studies set the stage for comparing the regulation by estrogen of their genes with that of vitellogenin genes in primary cultures of Xenopus oviduct cells and hepatocytes.

Animals↗
PubMed1991

Role of polyamine in the regulation of RNA synthesis in uterine nucleoli.

Administration of estradiol (E2) to ovariectomized mature rats has been shown to result in synthesis of uterine polyamines in the same temporal manner as E2 regulation of nucleolar transcription. Data is presented on the in vivo and in vitro effects of polyamines on uterine nucleolar RNA synthesis. Transcervical intrauterine administration of putrescine (100 micrograms), spermidine (100 micrograms), or spermine (100 micrograms) resulted in an increased transcriptional activity of 93 and 82% in uterine nucleoli isolated from putrescine and spermidine treated animals, respectively. Spermine administration was without effect on uterine nucleolar transcription. The polyamine-induced increase in transcription was totally accounted for by an increased rate of elongation of previously initiated RNA chains. No effect on the number of nucleolar RNA chains in the act of synthesis was observed. Preincubation of uterine nucleoli, isolated from control animals (no E2) with putrescine, spermidine, or spermine in the presence, but not in the absence of ATP, resulted in 44, 83 and 31% increased nucleolar RNA synthesis, respectively. In vitro polyamine-induced nucleolar RNA synthesis was correlated with a polyamine activated phosphorylation of nucleolar proteins of 110,000 24,000, 18,000 and 14,000 Da. Results suggest that early E2 action may result in activation of the polyamine pathway which modulates nucleolar protein kinase activity; initiating an increase in nucleolar transcription.

Adenosine Triphosphate↗