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Results for “RNA Regulation”

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At least 235 records · Page 13Linked to original sources
PubMed1994

The role of transcription factors, chromatin structure and DNA replication in 5 S RNA gene regulation.

Differential expression of the oocyte and somatic 5 S RNA genes during Xenopus development can be explained by changes in transcription factor and histone interactions with the two types of gene. Both factors and histones bind 5 S RNA genes with specificity. Protein-protein interactions determine the stability of potentially transcriptionally active or repressed nucleoprotein complexes. A decline in transcription factor abundance, differential binding of transcription factors to oocyte and somatic 5 S genes, and increased competition with the histones for association with DNA during early embryogenesis, can account for the developmental decision to selectively repress the oocyte genes, while retaining the somatic genes in the transcriptionally active state. The 5 S ribosomal genes of Xenopus are perhaps the simplest eukaryotic genes to show regulated expression during development. A large multigene family (oocyte 5 S DNA) is transcriptionally active in oocytes but is repressed in somatic cells, whereas a small multigene family (somatic 5 S DNA) is active in both cell types. A potential molecular mechanism to explain the developmental switch that turns off oocyte 5 S DNA transcription has been experimentally reconstructed in vitro and more recently tested in vivo. Central to this mechanism is the specific association of both transcription factors and histones with 5 S RNA genes. How the interplay of histones and transcription factors is thought to affect transcription, and how their respective contributions might change during development from an oocyte, to an embryo and eventually to a somatic cell is the focus of this review.

Animals↗
PubMed2005

ELL-associated factors 1 and 2 are positive regulators of RNA polymerase II elongation factor ELL.

In human cells, the ELL family of transcription factors includes at least three members, which are all capable of stimulating the overall rate of elongation by RNA polymerase II by suppressing transient pausing by the enzyme at many sites along DNA. In this report, we identify the ELL-associated factors (EAF)1 and EAF2 as strong positive regulators of ELL elongation activity. Our findings provide insights into the structure and function of ELL family transcription factors, and they bring to light direct roles for the EAF proteins in regulation of RNA polymerase II transcription.

Animals↗
PubMed1998

Drosophila ferritin mRNA: alternative RNA splicing regulates the presence of the iron-responsive element.

Several mRNAs encoding the same ferritin subunit of Drosophila melanogaster were identified. Alternative RNA splicing and utilisation of different polyadenylation sites were found to generate the transcripts. The alternative RNA splicing results in ferritin transcripts with four unique 5' untranslated regions. Only one of them contains an iron-responsive element. The iron-responsive element was found to bind in vitro specifically to human recombinant iron regulatory protein 1. Furthermore, the ferritin subunit mRNAs are differentially expressed during development. Our data provides the first molecular evidence that the presence of iron-responsive element in a ferritin mRNA is regulated by alternative RNA splicing.

Alternative Splicing↗
PubMed2002

Clostridial VirR/VirS regulon involves a regulatory RNA molecule for expression of toxins.

We analysed the region encoding VR-RNA (VirR-regulated RNA), which has been reported to be positively regulated by the two-component VirR/VirS system in Clostridium perfringens. The VR-RNA promoter identified by primer extension analysis was preceded by a probable VirR-binding site (CCAGTTNNNCAC), which resembled a repeated sequence motif present in the promoter region of the theta-toxin (pfoA) gene. A VR-RNA-null mutant, constructed by a homologous recombination, exhibited a reduced amount of transcription of the alpha- (plc) and kappa-toxin (colA) genes, which was restored by the complementation of intact VR-RNA, indicating that the VR-RNA region plays an important role in the regulation of the plc and colA genes in C. perfringens. It was found that the regulatory effect was observed even when the hyp7 gene encoded on VR-RNA was deleted or a nonsense mutation was introduced in the hyp7-coding region. We found that the small 3'-portion of VR-RNA was sufficient for the activation of toxin genes, which suggested that VR-RNA itself could act as an RNA regulatory molecule for the plc and colA genes mediating the regulatory information from the VirR/VirS system in C. perfringens.

Amino Acid Sequence↗
PubMedDate not supplied

Direct regulation of RNA polymerase III transcription by RB, p53 and c-Myc.

The synthesis of tRNA and 5S rRNA by RNA polymerase (pol) III is cell cycle regulated in higher organisms. Overexpression of pol III products is a general feature of transformed cells. These observations may be explained by the fact that a pol III-specific transcription factor, TFIIIB, is strongly regulated by the tumor suppressors RB and p53, as well as the proto-oncogene product c-Myc. RB and p53 repress TFIIIB, but this restraint can be lost in tumors through a variety of mechanisms. In contrast, c-Myc binds and activates TFIIIB, causing potent induction of pol III transcription. Using chromatin immunoprecipitation and RNA interference, we show that c-Myc interacts with tRNA and 5S rRNA genes in transformed cervical cells, stimulating their expression. Availability of pol III products may be an important determinant of a cell's capacity to grow. The ability to regulate pol III output may therefore be integral to the growth control functions of RB, p53 and c-Myc.

Animals↗
PubMed1978

Hormonal activation of adenylate cyclase and its role in cyclic AMP mediated regulation of RNA synthesis in the mouse mammary gland.

The activity of adenylate cyclase (EC 4.6.1.1) in the mouse mammary gland increases during late pregnancy and reaches its maximum value at one day pre partum. In the mouse mammary gland explant culture the adenylate cyclase activity is stimulated by a cooperative action of insulin, prolactin and hydrocortisone. The effect of these hormones can be demonstrated in intact cells, but not in a cell-free system. In the explants, RNA synthesis is stimulated by dibutyryl cyclic AMP, insulin and prolactin. The effects of both protein hormones and cyclic AMP are additive. The results obtained suggest that insulin and prolactin in cooperation with hydrocortisone are involved in the regulation of RNA synthesis in the mammary gland by activation of the adenylate cyclase system, independently of their effect on this process not mediated by cyclic AMP.

Adenylyl Cyclases↗
PubMed2004

Pinning down transcription: regulation of RNA polymerase II activity during the cell cycle.

Pin1 is a peptidyl-prolyl cis/trans isomerase that was initially discovered as an important mitotic regulator. In keeping with this, it targets specifically phosphorylated ser- or thr-pro dipeptides, which are found in numerous mitotic proteins as a result of cyclin-dependent kinase activity. But Pin1 also modulates the activity of numerous other proteins, and a strong candidate for such regulation has been RNA polymerase II (RNAP II). The unique C-terminal domain of the RNAP II largest subunit contains as many as 100 ser-pro dipeptides laid out in an essentially linear array, and which are subject to different patterns of phosphorylation. Here we summarize findings indicating that Pin1 can indeed directly modulate the structure and function of RNAP II, and propose that this activity plays a role both in mitotic gene silencing and during the transcription cycle.

Aspergillus↗
PubMed1995

Cell cycle regulation of RNA polymerase III transcription.

Inactivation of the TATA-binding protein-containing complex TFIIIB contributes to the mitotic repression of RNA polymerase III transcription, both in frogs and in humans (J. M. Gottesfeld, V. J. Wolf, T. Dang, D. J. Forbes, and P. Hartl, Science 263:81-84, 1994; R. J. White, T. M. Gottlieb, C. S. Downes, and S. P. Jackson, Mol. Cell. Biol. 15:1983-1992, 1995). Using extracts of synchronized proliferating HeLa cells, we show that TFIIIB activity remains low during the early part of G1 phase and increases only gradually as cells approach S phase. As a result, the transcription of all class III genes tested is significantly less active in early G1 than it is in S or G2 phase, both in vitro and in vivo. The increased activity of TFIIIB as cells progress through interphase appears to be due to changes in the TATA-binding protein-associated components of this complex. The data suggest that TFIIIB is an important target for the cell cycle regulation of RNA polymerase III transcription during both mitosis and interphase of actively proliferating HeLa cells.

Cell Cycle↗
PubMed1993

A phylogenetically conserved sequence within viral 3' untranslated RNA pseudoknots regulates translation.

Both the 68-base 5' leader (omega) and the 205-base 3' untranslated region (UTR) of tobacco mosaic virus (TMV) promote efficient translation. A 35-base region within omega is necessary and sufficient for the regulation. Within the 3' UTR, a 52-base region, composed of two RNA pseudoknots, is required for regulation. These pseudoknots are phylogenetically conserved among seven viruses from two different viral groups and one satellite virus. The pseudoknots contained significant conservation at the secondary and tertiary levels and at several positions at the primary sequence level. Mutational analysis of the sequences determined that the primary sequence in several conserved positions, particularly within the third pseudoknot, was essential for function. The higher-order structure of the pseudoknots was also required. Both the leader and the pseudoknot region were specifically recognized by, and competed for, the same proteins in extracts made from carrot cell suspension cells and wheat germ. Binding of the proteins is much stronger to omega than the pseudoknot region. Synergism was observed between the TMV 3' UTR and the cap and to a lesser extent between omega and the 3' UTR. The functional synergism and the protein binding data suggest that the cap, TMV 5' leader, and 3' UTR interact to establish an efficient level of translation.

Base Sequence↗
PubMed2026

RNA structures regulate norovirus life cycle and enable rational attenuation in vivo.

Viral genomes encode regulatory RNA structures that orchestrate key steps of viral replication and gene expression. Although these structures are increasingly recognized as critical regulators of viral function, their systematic characterization in an infection context and roles in regulating viral fitness and immune recognition in vivo remain limited. Here, we systematically map and functionally interrogate structured RNA elements across the murine norovirus genome using orthogonal in-cell chemical probing, revealing conserved motifs that regulate viral function. Targeted disruption of specific structural elements reduces viral replication in cell culture, modulates translation in cis, and decreases viral RNA levels in animal infection models. These findings enabled the rational design of a genetically stable, attenuated virus that elicits protective immunity and limits viral replication upon secondary challenge. Together, this work uncovers essential roles for RNA structure in norovirus biology and establishes a generalizable framework for RNA structure-guided design of antiviral vaccines and therapeutics.

RNA structure↗
PubMed1989

Do ribosomes regulate mitochondrial RNA synthesis?

The levels of different classes of mitochondrially encoded transcripts are developmentally regulated in sea urchin embryos, as a result of selection between mutually exclusive synthetic pathways. I propose a simple model to explain these observations, based on a dual role for mitochondrial ribosomes and translation factors in RNA synthesis as well as in translation. This effect may be exerted either at the transcriptional or post-transcriptional level (or both), and is potentially generalizable to mammalian mtDNA and to other systems.

Animals↗
PubMed1977

The regulation of RNA synthesis in yeast II: Amino acids shift-up experiments.

A study has been made of the effects of a casamino acids shift-up on a prototrophic strain of yeast growing under conditions of ammonium repression. The shift-up produced an increase in growth rate some 120 min after the addition of amino acids to the medium. This growth rate increase was slightly preceded by an increase in the rate of accumulation of DNA. In contrast, the rate of accumulation of protein increased immediately and that of RNA 15-20 min after the shift. RNA was initially accumulated at a rate greater than that required to sustain the new steady state. This was shown to be due to an increase in the rate of synthesis of the rRNA species derived from the 35S precursor. The rate of synthesis of 5S rRNA and of tRNA increased much later and to a lesser extent than that of the 35S derived species. The implications of these results for general theories of regulation of RNA synthesis are discussed.

Amino Acids↗
PubMed1994

Polyadenylation of the mRNA of hepatitis delta virus is dependent on the structure of the nascent RNA and regulated by the small or large delta antigen.

During the hepatitis delta virus (HDV) RNA replication, synthesis of either the mRNA for the delta antigen (HDAg) or the full-length antigenomic RNA is determined by selective usage of the potent poly(A) signal on the antigenome. To elucidate the regulatory mechanism, HDV cDNA cotransfection system was used to examine the potential effect of the secondary structure of the nascent RNA and that of the HDAg on HDV polyadenylation in transfected cells. We found that when the nascent RNA species could fold itself to form the rodlike structure, the HDV polyadenylation was suppressed 3 to 5 fold by the HDAg. In addition, we observed that the small and the large HDAg exerted a similar suppressive effect on the HDV polyadenylation, though they played different roles in HDV replication. We concluded that the HDV polyadenylation could be regulated by the structure of the nascent antigenomic RNA and by either the small or large HDAg.

Antigens, Viral↗
PubMed1986

Cloning of estrogen-regulated messenger RNA sequences from human breast cancer cells.

A complementary DNA library was constructed from RNA of estrogen-stimulated MCF-7 cells and screened for estrogen-regulated sequences. Four different messenger RNA sequences of varying abundance were isolated. Two of the sequences (pNR-3 and pNR-4) were induced approximately 2-fold, while the other two (pNR-1 and pNR-2) were induced at least 8-fold. The induction of both pNR-1 and pNR-2 requires similar physiological concentrations of estradiol and is near maximal at 10(-10) M. An increase in the levels of the RNAs is seen after 30 min of estrogen treatment, but pNR-1 reaches its maximal concentration faster than pNR-2. pNR-1 and pNR-2 were not expressed in all human breast cancer cell lines tested. pNR-1 was expressed and regulated by estrogen in the estrogen receptor-positive cell lines, MCF-7, T-47D, and ZR 75, whereas pNR-2 was not expressed in the T-47D cell line. pNR-1 and pNR-2 were not detected in two estrogen receptor-negative cell lines (BT20 and HBL 100). As the proliferation of the MCF-7, T47D, and ZR 75 cell lines is stimulated by estradiol, pNR-1 may provide a useful marker of hormone-responsive breast cancer.

Base Sequence↗
PubMed1998

Nucleocytoplasmic transport of HTLV-1 RNA is regulated by two independent LTR encoded nuclear retention elements.

Appropriate expression of HTLV-1 genes requires transcriptional transactivation by Tax and post-transcriptional regulation by Rex, both mediated by LTR encoded RNA sequences. Using a combination of deletion mutagenesis, Rex-reporter CAT assays, fluorescence in situ hybridization (FISH) and confocal laser scanning microscopy it was established that in the absence of Rex, CAT mRNAs harboring HTLV-1 LTR sequences were unable to leave the nucleus. Deletion of the known U5 encoded cis-acting repressing sequence (CRS) led to a partial release of nuclear retention. A novel regulatory element overlapping the 3' Rex responsive element (RxRE) region was shown to prevent export and expression of these transcripts. Deletion of both the 5' LTR encoded CRS and 3' LTR encoded downstream repressive sequence (3' CRS) led to constitutive mRNA nuclear export and gene expression, independently of Rex. The locations of the two regulatory elements indicate that while the 5' CRS selectively acts to hinder export of unspliced transcripts, the 3' CRS has the capacity to induce nuclear retention of all HTLV-1 transcripts, and therefore could potentially contribute to viral latency in infected cells.

Animals↗
PubMed2003

Down-regulation of RNA helicase II/Gu results in the depletion of 18 and 28 S rRNAs in Xenopus oocyte.

Genetic manipulations have revealed the functions of RNA helicases in ribosomal RNA (rRNA) biogenesis in yeast. However, no report shows the role of an RNA helicase in rRNA formation in higher eukaryotes. This study reports the functional characterization of the frog homologue of nucleolar RNA helicase II/Gu (xGu or DDX21). Down-regulation of xGu in Xenopus laevis oocyte using an antisense oligodeoxynucleotide results in the depletion of 18 and 28 S rRNAs. The disappearance of 18 S rRNA is accompanied by an accumulation of 20 S, indicating that xGu is critical in the processing of 20 to 18 S rRNA. The degradation of 28 S rRNA into fragments smaller than 18 S is also associated with a specific decrease in the level of xGu protein. These effects are reversed in the presence of in vitro synthesized wild type xGu mRNA but not its helicase-deficient mutant form. Similar aberrant rRNA processing is observed when antibody against xGu is microinjected. The involvement of xGu in processing of rRNA is consistent with the localization of Gu protein to the granular and dense fibrillar components of PtK2 cell nucleoli by immunoelectron microscopy. Our results show that xGu is involved in the processing of 20 to 18 S rRNA and contributes to the stability of 28 S rRNA in Xenopus oocytes.

Amino Acid Sequence↗
PubMed2002

Characterization of the small antisense CI RNA that regulates bacteriophage P4 immunity.

In the immune state bacteriophage P4 prevents expression of the replication functions by premature termination of transcription. A small RNA, the CI RNA, is the trans acting factor that regulates P4 immunity, by pairing to complementary target sequences and causing premature transcription termination. The CI RNA is matured by RNAse P and PNPase from the leader region of the same operon it regulates. In this work we better characterize this molecule. CI RNA copy number was determined to be around 500 molecules per lysogenic cell. By S(1) mapping we defined the 3'-end at 8423(+/-1); thus CI RNA is 79(+/-1) nt long. The minimum region for correct processing requires two bases upstream of the CI RNA 5'-end and the CCA sequence at the 3'-end. Computer analysis by FOLD RNA of CI RNA sequence predicts a cloverleaf-like structure formed by a double-stranded stalk, a minor and a major stem loop, and a single-stranded bulge. We analysed several cI mutations, which fall either in the single or double-stranded CI RNA regions. Base substitutions in the main loop and in the single-stranded bulge apparently did not change CI RNA structure, but affected its activity by altering the complementarity with the target sequences, whereas a mutation in the secondary stem had a disruptive effect on CI RNA secondary structure. The effects of this latter mutation were suppressed by a base substitution that restored the complementarity with the corresponding base in the stem. Base substitutions in the main stem caused only local alterations in the secondary structure of CI. However, when the substitutions concerned either G8501 or its complementary base at the bottom of the stem, CI RNA was not correctly processed.

Base Sequence↗
PubMed1990

Phorbol ester treatment down-regulates immunoglobulin RNA steady-state levels in B type chronic lymphocytic leukemia and non-Hodgkin's lymphoma cells.

The human B-lymphoma cell lines BJAB and Daudi, as well as the human pre-B cell line KM3, were found to down-regulate steady-state immunoglobulin RNA levels 2- to 4-fold after stimulation with phorbol 12-myristate-13-acetate (PMA) for 24 hr. No down-regulation of the transcriptional rate of a kappa promoter could be observed in any of these cell lines upon transient expression transfection. The observed down-regulation of steady-state immunoglobulin RNA affected both the secretory and the membrane form of the mu transcript equally. When freshly isolated chronic lymphocytic leukemia (CLL) cells where tested for their response to PMA, three of four isolates responded by down-regulating their steady-state immunoglobulin RNA levels.

Animals↗