Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “RNA Regulation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,081 records · Page 60Linked to original sources
PubMed2025

Oncogenic DEAD-box ATPase DDX41 establishes transcript ensembles via CLK3-dependent and -independent mechanisms.

Post-transcriptional diversification of RNA transcripts mediated by complex processing machinery, including DEAD-box ATPases, establishes and maintains cellular phenotypes. For example, DDX41 controls RNA splicing, innate immune signaling, and genome stability. Although heterozygous DDX41 germline genetic variation occurs in familial myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), the DDX41 contributions to splicing globally, biological processes, and pathogenic mechanisms are incompletely defined. Using a genetic rescue system with Ddx41+/- myeloid progenitors, we established global wildtype DDX41 and pathogenic variant mechanisms. Differing from pathogenic variants of other RNA splicing regulators, DDX41 deficiency compromised multiple splicing steps. DDX41-regulated transcripts encoded factors controlling RNA splicing, including Cdc2-like kinase 3 (CLK3). DDX41 regulated Clk3 transcripts, and elevated CLK3 during myeloid differentiation. Loss-of-function analysis revealed DDX41-regulated splicing commonly, but not always, required CLK3. Thus, through a mechanism utilizing a splicing factor kinase that itself is DDX41-regulated, DDX41 establishes transcript ensembles in myeloid progenitors.

DEAD-box RNA Helicases↗
PubMed1999

Multiple layers of cooperativity regulate enhanceosome-responsive RNA polymerase II transcription complex assembly.

Two coordinate forms of transcriptional synergy mediate eukaryotic gene regulation: the greater-than-additive transcriptional response to multiple promoter-bound activators, and the sigmoidal response to increasing activator concentration. The mechanism underlying the sigmoidal response has not been elucidated but is almost certainly founded on the cooperative binding of activators and the general machinery to DNA. Here we explore that mechanism by using highly purified transcription factor preparations and a strong Epstein-Barr virus promoter, BHLF-1, regulated by the virally encoded activator ZEBRA. We demonstrate that two layers of cooperative binding govern transcription complex assembly. First, the architectural proteins HMG-1 and -2 mediate cooperative formation of an enhanceosome containing ZEBRA and cellular Sp1. This enhanceosome then recruits transcription factor IIA (TFIIA) and TFIID to the promoter to form the DA complex. The DA complex, however, stimulates assembly of the enhanceosome itself such that the entire reaction can occur in a highly concerted manner. The data reveal the importance of reciprocal cooperative interactions among activators and the general machinery in eukaryotic gene regulation.

Allosteric Regulation↗
PubMed2002

The Scw1 RNA-binding domain protein regulates septation and cell-wall structure in fission yeast.

Loss of the nonessential RNA-binding domain protein, Scw1, increases resistance to cell-wall-degrading enzymes in fission yeast. Surprisingly, scw1 null mutations also suppress the lethality of mutations (cdc11-136, cdc7-24, cdc14-118, sid1-239, sid2-250, sid3-106, sid4-A1, and mob1-1) at all levels of the sid pathway. This pathway forms part of the septation initiation network (SIN), which regulates the onset of septum formation and ensures the proper coupling of mitosis to cytokinesis. In contrast, scw1(-) mutations do not suppress ts alleles of the rng genes, cdc12 or cdc15. These mutations also prevent the formation of a septum and in addition block assembly and/or function of the contractile acto-myosin ring. sid mutants exhibit a hyper-sensitivity to cell-wall-degrading enzymes that is suppressed by loss of Scw1. Furthermore, scw1(-)-mediated rescue of sid mutants is abolished in the presence of calcofluor white, a compound that interferes with cell-wall synthesis. These data suggest that Scw1 acts in opposition to the SIN as a negative regulator of cell-wall/septum deposition. Unlike components of the SIN, Scw1 is predominantly a cytoplasmic protein and is not localized to the spindle pole body.

Amino Acid Sequence↗
PubMed2001

Hfq is necessary for regulation by the untranslated RNA DsrA.

DsrA is an 85-nucleotide, untranslated RNA that has multiple regulatory activities at 30 degrees C. These activities include the translational regulation of RpoS and H-NS, global transcriptional regulators in Escherichia coli. Hfq is an E. coli protein necessary for the in vitro and in vivo replication of the RNA phage Qbeta. Hfq also plays a role in the degradation of numerous RNA transcripts. Here we show that an hfq mutant strain is defective for DsrA-mediated regulation of both rpoS and hns. The defect in rpoS expression can be partially overcome by overexpression of DsrA. Hfq does not regulate the transcription of DsrA, and DsrA does not alter the accumulation of Hfq. However, in an hfq mutant, chromosome-expressed DsrA was unstable (half-life of 1 min) and truncated at the 3' end. When expressed from a multicopy plasmid, DsrA was stable in both wild-type and hfq mutant strains, but it had only partial activity in the hfq mutant strain. Purified Hfq binds DsrA in vitro. These results suggest that Hfq acts as a protein cofactor for the regulatory activities of DsrA by either altering the structure of DsrA or forming an active RNA-protein complex.

Bacterial Proteins↗
PubMed1979

Regulation of herpesvirus macromolecular synthesis. VIII. The transcription program consists of three phases during which both extent of transcription and accumulation of RNA in the cytoplasm are regulated.

This report concerns the stable viral RNA sequences that accumulate in HEp-2 cells infected with herpes simplex virus type 1. By hybridizing labeled total DNA and restriction endonuclease DNA fragments with excess unlabeled total nuclear and cytoplasmic RNA, we determined the genetic complexity of the RNA and we mapped the regions on the physical map of herpes simplex virus type 1 DNA that are homologous to the RNA. Our results show the following. (i) The viral RNAs accumulating in the nucleus and cytoplasm of cells infected and maintained in the presence of inhibitory concentrations of either cycloheximide or emetine were homologous to 33 and 12% of viral DNA, respectively. All of the fragments tested contained sequences homologous to nuclear RNA. However, only the fragments mapping between 0.00 and 0.18, and 0.53 and 1.00 map units contained sequences homologous to cytoplasmic RNA. (ii) The viral RNAs that accumulate in the nucleus and cytoplasm of cells infected and maintained in the presence of inhibitory concentrations of phoaphonoacetic acid were homologous to 39 and 26% of viral DNA, respectively. In this instance all of the fragments except those mapping between 0.42 and 0.53 map units contained sequences homologous to cytoplasmic RNA. (iii) The viral RNAs that accumulate in the nucleus and cytoplasm 8 h after infection were homologous to greater than 50 and 41%, respectively. All of the fragments tested contained sequences homologous to cytoplasmic RNA. (iv) The viral RNAs that accumulate in the nucleus and cytoplasm of cells infected and maintained in the presence of canavanine are homologous to 33 and 19% of viral DNA, respectively. All of the fragments tested contained sequences homologous to both nuclear and cytoplasmic RNAs. Our results indicate the following. First, there are at least three phases of transcription of viral DNA. Phase 1 does not require the synthesis of host cell or viral proteins. Phase 2 requires the synthesis of viral proteins made before the initiation of viral DNA synthesis. Phase 3 appears to be related to the initiation of viral DNA synthesis. Second, both the extent of transcription and the accumulation of viral RNA in the cytoplasm are tightly regulated. The genetic complexity of total RNA accumulating in infected cells increased in each successive phase. Moreover, the genetic complexity of nuclear RNA was invariably higher than that of cytoplasmic RNA in each phase. Lastly, the results of the studies on viral RNA accumulating in canavanine-treated cells reinforce the hypothesis made previously that more than one polypeptide in each of the alpha and beta polypeptide groups is involved in the transcription preceding the transitions from alpha to beta and beta to gamma polypeptide synthesis, respectively, and that canavanine selectively inactivated subsets of these polypeptides permitting only partial transitions from alpha to beta and beta to gamma to occur.

Base Sequence↗
PubMed1997

The trp RNA-binding attenuation protein regulates TrpG synthesis by binding to the trpG ribosome binding site of Bacillus subtilis.

The trpG gene of Bacillus subtilis encodes a glutamine amidotransferase subunit which is involved in the biosynthesis of L-tryptophan and folic acid. The trp RNA-binding attenuation protein (TRAP) is involved in controlling expression of trpG at the level of translation in response to changes in the intracellular concentration of tryptophan. We performed in vitro experiments using purified TRAP to elucidate the mechanism of TRAP-dependent trpG regulation. A TRAP-trpG RNA footprint analysis showed that tryptophan-activated TRAP interacts with one UAG, one AAG, and seven GAG repeats present in the trpG transcript. Results from ribosome and TRAP toeprint experiments indicated that the ribosome and TRAP binding sites overlap. Experiments with a B. subtilis cell-free translation system demonstrated that TRAP inhibits TrpG synthesis. Thus, TRAP regulates translation of trpG by blocking ribosome access to the trpG ribosome binding site. Our results are consistent with a model in which each tryptophan-activated TRAP subunit interacts with one trinucleotide repeat in an RNA target, thereby wrapping the transcript around the periphery of the TRAP complex.

Anthranilate Synthase↗
PubMed2002

A surveillance system regulates selective entry of RNA into the shoot apex.

Phloem-mobile endogenous RNA is trafficked selectively into the shoot apex. In contrast, most viruses and long-distance post-transcriptional gene silencing (PTGS) signals are excluded from the shoot apex. These observations suggest the operation of an underlying regulatory mechanism. To examine this possibility, a potexvirus movement protein, known to modify cell-to-cell trafficking and PTGS, was expressed ectopically in transgenic plants. These plants were found to be compromised in their capacity to exclude both viral RNA and silencing signals from the shoot apex. The transgenic plants also displayed various degrees of abnormal leaf polarity depending on transgene expression level. Normal patterns of organ development were restored by either virus- or Agrobacterium tumefaciens-mediated induction of PTGS. This revealed the presence of an RNA signal surveillance system that acts to allow the selective entry of RNA into the shoot apex. We propose that this surveillance system regulates signaling and protects the shoot apex, in particular the cells that give rise to reproductive structures, from viral invasion.

Cloning, Molecular↗
PubMed1998

ncl-1 is required for the regulation of cell size and ribosomal RNA synthesis in Caenorhabditis elegans.

Regulation of ribosome synthesis is an essential aspect of growth control. Thus far, little is known about the factors that control and coordinate these processes. We show here that the Caenorhabditis elegans gene ncl-1 encodes a zinc finger protein and may be a repressor of RNA polymerase I and III transcription and an inhibitor of cell growth. Loss of function mutations in ncl-1, previously shown to result in enlarged nucleoli, result in increased rates of rRNA and 5S RNA transcription and enlarged cells. Furthermore, ncl-1 adult worms are larger, have more protein, and have twice as much rRNA as wild-type worms. Localization studies show that the level of NCL-1 protein is independently regulated in different cells of the embryo. In wild-type embryos, cells with the largest nucleoli have the lowest level of NCL-1 protein. Based on these results we propose that ncl-1 is a repressor of ribosome synthesis and cell growth.

Amino Acid Sequence↗
PubMed1991

RNA polymerase activity may regulate transcription initiation and attenuation in the rplKAJLrpoBC operon in Escherichia coli.

The relationship between global RNA transcription capacity and transcript initiation, attenuation, and stability in the rplKAJLrpoBC operon of Escherichia coli has been examined. The rplKAJLrpoBC operon encodes in order the four large ribosome subunit proteins, L11, L1, L10, and L12, and the two large beta and beta' subunits of RNA polymerase. Operon transcripts are initiated at two promoters, PL11 and PL10. The L12-beta intergenic space contains a transcription attenuator which, during balanced growth, terminates about 80% of the transcripts exiting the L12 gene; the remaining transcripts read through into the beta and beta' encoding genes. The capacity for global transcription initiation was modulated using a strain carrying a temperature-sensitive, initiation-defective mutation in rpoC. Following a shift to 39 degrees C, the global transcription initiation capacity was reduced to about one-half the level at 30 degrees C. This partial restriction resulted in a decrease in the stability of distal beta mRNA, whereas the stability of proximal L11-L1 and L10-L12 mRNA was not changed. Measurements of the synthesis rates of L11-L1, L10-L12, and beta mRNAs relative to total RNA synthesis indicated that this operon was selectively transcribed when the initiation capacity of RNA polymerase was limited. The synthesis rates of L11-L1 and L10-L12 mRNA increased about 2-fold, whereas the synthesis rate of beta mRNA increased nearly 5-fold. The relative transcription of other ribosome component genes and the alpha subunit gene exhibited only a modest increase during the partial restriction. Protection from S1 nuclease was used to demonstrate that the preferential transcription within the operon of beta mRNA was the consequence of active regulation of termination-antitermination at the attenuator structure in the L12-beta intergenic space. These results demonstrate that global transcription capacity may be an important parameter in determining both initiation and attenuation of transcription of the rplKAJLrpoBC ribosomal protein-RNA polymerase operon.

Base Sequence↗
PubMed1994

Regulation of influenza virus RNA polymerase activity by cellular and viral factors.

An in vitro RNA synthesis system mimicking replication of genomic influenza virus RNA was developed with nuclear extracts prepared from influenza virus-infected HeLa cells using exogenously added RNA templates. The RNA synthesizing activity was divided into two complementing fractions, i.e. the ribonucleoprotein (RNP) complexes and the fraction free of RNP, which could be replaced with RNP cores isolated from virions and nuclear extracts from uninfected cells, respectively. When nuclear extracts from uninfected cells were fractionated by phosphocellulose column chromatography, the stimulatory activity for RNA synthesis was further separated into two distinct fractions. One of them, tentatively designated RAF (RNA polymerase activating factor), stimulated RNA synthesis with either RNP cores or RNA polymerase and nucleocapsid protein purified from RNP cores as the enzyme source. In contrast, the other, designated PRF (polymerase regulating factor), functioned as an activator only when RNP cores were used as the enzyme source. Biochemical analyses revealed that PRF facilitates dissociation of RNA polymerase from RNP cores. Of interest is that virus-coded non-structural protein 1 (NS1), which has been thought to be involved in regulation of replication, counteracted PRF function. Roles of cellular factors and viral proteins, NS1 in particular, are discussed in terms of regulation of influenza virus RNA genome replication.

Biological Factors↗
PubMed2003

Essential steps in the ppGpp-dependent regulation of bacterial ribosomal RNA promoters can be explained by substrate competition.

Transcription of stable RNA genes is known to be dramatically reduced in the presence of guanosine tetraphosphate (ppGpp), the mediator of the stringent response. Using in vitro transcription systems with ribosomal RNA P1 promoters, we have analyzed which step of the initiation cycle is inhibited by the effector ppGpp. We show that formation of the ternary transcription initiation complex consisting of RNA polymerase holoenzyme, the promoter DNA, and the first initiating nucleotide triphosphate is the major step at which ppGpp exerts its regulation. Neither primary binding of RNA polymerase to the promoter nor isomerization to the open binary complexes or the subsequent promoter clearance steps contributes notably to the observed inhibition. The effect of ppGpp-dependent inhibition in the formation of the ternary transcription initiation complex could be mimicked by nucleotide derivatives known to bind to the RNA polymerase active center. Using these model compounds, almost identical inhibition characteristics were observed as seen with ppGpp. The results support the previously published model, which suggests that ppGpp-dependent inhibition is based on competition between the inhibitor molecules and NTP substrates for access to the active center of RNA polymerase.

DNA-Directed RNA Polymerases↗
PubMed2000

Developmental regulation of tryptophan hydroxylase messenger RNA expression and enzyme activity in the raphe and its target fields.

Tryptophan hydroxylase is the rate-limiting enzyme in the synthesis of serotonin and during development, brain serotonin levels and tryptophan hydroxylase activities increase. Increased tryptophan hydroxylase activity could result from alterations in tryptophan hydroxylase messenger RNA levels, translation, and/or post-translational regulation. Tryptophan hydroxylase messenger RNA levels in the dorsal raphe nucleus increased 35-fold between embryonic day 18 and postnatal day 22, measured by quantitative in situ hybridization, then decreased by 40% between postnatal days 22 and 61. These changes correlated with tryptophan hydroxylase enzyme activities in the raphe nuclei as expected, but not in cortical or hippocampal targets. Tryptophan hydroxylase messenger RNA expression in the nucleus raphe obscuris increased 2.5-fold between postnatal days 8 and 22 but did not correlate with enzyme activity in the spinal cord. Using an in vitro model of serotonergic raphe neuron differentiation, serotonergic differentiation was associated with an increase in both tryptophan hydroxylase promoter activity and protein expression. In vivo, tryptophan hydroxylase messenger RNA levels per single cell and per brain section were correlated during development up to postnatal day 22, but not beyond for both the dorsal raphe nucleus and nucleus raphe obscuris. Between postnatal days 22 and 61 single cell levels of tryptophan hydroxylase messenger RNA in the dorsal raphe nucleus did not change yet the levels per brain section significantly decreased by 40%. During the same period in the nucleus raphe obscuris, tryptophan hydroxylase messenger RNA levels per single cell signifcantly increased by 30% yet levels per brain section did not change. Comparison of tryptophan hydroxylase messenger RNA levels per cell and per brain section indicated a serotonergic loss between postnatal days 22 and 61 in both the dorsal raphe nucleus and nucleus raphe obscuris and may reflect either a loss of neurotransmitter phenotype or cell death. This study is the first to characterize the expression of brain tryptophan hydroxylase messenger RNA during rat development. In addition, this study is the first to report the activity of tryptophan hydroxylase in the spinal cord and hippocampus in the embryonic and neonatal rat. Together, the data provide a better understanding of the intricate relationship between patterns of tryptophan hydroxylase messenger RNA expression and enzyme activity.

Age Factors↗
PubMed1996

Acute and chronic noradrenergic regulation of neurotrophin messenger RNA expression in rat hippocampus: evidence from lesions and organotypic cultures.

Noradrenergic neurons from the locus coeruleus innervate several brain regions, such as hippocampus and cortex. The hippocampus exhibits the highest concentration of the neurotrophins nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in the brain. To study the role of the noradrenergic system in the chronic regulation of neurotrophin messenger RNA expression, chemical [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, 6-hydroxydopamine] and mechanical (knife-cut axotomy) lesions were performed, in the rat, and neurotrophin messenger RNAs analysed after 14 and 35 days. The intensity of the lesion was verified by characterization of the noradrenergic system using immunohistochemistry and in situ hybridization for dopamine-beta-hydroxylase and the measurement of noradrenaline tissue levels. To study the acute regulation, hippocampal organotypic slice cultures were prepared and neurotrophin messenger RNAs analysed after incubation in different concentrations of noradrenaline. We report that the noradrenergic N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine depletion significantly increased nerve growth factor and brain-derived neurotrophic factor messenger RNAs but not neurotrophin-3 messenger RNA in hippocampal areas 35 days after the lesion, while the knife-cut axotomy had a less pronounced effect and the 6-hydroxydopamine lesion did not change the neurotrophins. When incubating the organotypic hippocampal cultures with different concentrations of noradrenaline, nerve growth factor and brain-derived neurotrophic factor messenger RNAs but not neurotrophin-3 messenger RNA were significantly reduced in the dentate gyrus. We conclude that nerve growth factor and brain-derived neurotrophic factor but not neurotrophin-3 expression are inhibited by noradrenaline, arising from the locus coeruleus.

Animals↗
PubMed2005

mTOR function in skeletal muscle hypertrophy: increased ribosomal RNA via cell cycle regulators.

The purpose of this study was to identify the potential downstream functions associated with mammalian target of rapamycin (mTOR) signaling during myotube hypertrophy. Terminally differentiated myotubes were serum stimulated for 3, 6, 12, 24, and 48 h. This treatment resulted in significant myotube hypertrophy (protein/DNA) and increased RNA content (RNA/DNA) with no changes in DNA content or indices of cell proliferation. During myotube hypertrophy, the increase in RNA content was accompanied by an increase in tumor suppressor protein retinoblastoma (Rb) phosphorylation and a corresponding increase in the availability of the ribosomal DNA transcription factor upstream binding factor (UBF). Serum stimulation also induced an increase in cyclin D1 protein expression in the differentiated myotubes with a concomitant increase in cyclin D1-dependent cyclin-dependent kinase (CDK)-4 activity toward Rb. The increases in myotube hypertrophy and RNA content were blocked by rapamycin treatment, which also prevented the increase in cyclin D1 protein expression, CDK-4 activity, Rb phosphorylation, and the increase in UBF availability. Our findings demonstrate that activation of mTOR is necessary for myotube hypertrophy and suggest that the role of mTOR is in part to modulate cyclin D1-dependent CDK-4 activity in the regulation of Rb and ribosomal RNA synthesis. On the basis of these results, we propose that common molecular mechanisms contribute to the regulation of myotube hypertrophy and growth during the G1 phase of the cell cycle.

Animals↗
PubMed1988

Developmentally regulated slow troponin C messenger RNA in chicken skeletal and cardiac muscles.

Regulation of slow troponin C gene expression was examined in both skeletal and cardiac muscle at various stages of development in chicken. The steady-state levels of troponin C mRNA were initially measured by Northern blot analysis. It was observed that the level of troponin C mRNA reached its maximum in both skeletal and cardiac muscle of 16- to 18-day-old embryos. A drop in troponin C mRNA level was observed just prior to hatching. The level of actin mRNA, myosin heavy chain mRNA, and mRNA for a nonmuscle protein, vimentin, was also similarly regulated during development of chicken muscles. Further studies were carried out to determine the level of slow troponin C mRNA using nuclease S1 protection analysis. A significant amount of slow troponin C mRNA was found in the skeletal muscle of adult chicken, which predominantly consists of the fast isoform of troponin C. This observation suggests the possibility of post-transcriptional control of slow troponin C synthesis in skeletal muscle. Primary cultures of cardiac myocytes were also used to determine how the troponin C mRNA level is regulated in a culture of cardiac muscle cells. Measurements of the steady-state levels of slow troponin C mRNA by nuclease S1 protection analysis show that it was maximal in 60-h-old cultures. A drop in the level of this mRNA was observed after these cells were maintained in culture for 4 days.

Actins↗
PubMed2005

Translational regulation of MOS messenger RNA in pig oocytes.

The temporal and spatial translation control of stored mRNA in oocytes is regulated by elements in their 3'-untranslated region (3'-UTR). The MOS 3'-UTR in pig oocytes is both heterogeneous (180, 480, or 530 nucleotides), and it contains multiple U-rich elements and extensive A-rich sequences (CA13CA5CA5CA6). We have examined the role of these potential regulatory elements by fusing wild-type or mutant MOS 3'-UTRs to luciferase mRNA and then injecting these chimeric transcripts into oocytes. We draw six main conclusions. First, the length of the MOS 3'-UTR tightly controls the level of translation of luciferase during oocyte maturation. Second, two U-rich (U5A) elements and the hexanucleotide signal (AAUAAA) are required for translation. Third, mutations, duplications, or relocations of the A-rich sequence reduce or block translation. Fourth, the relative importance of the A-rich and U-rich elements in controlling the level of translation differs. Fifth, none of our MOS 3'-UTR manipulations relieved translational repression before germinal vesicle breakdown. Sixth, all the MOS mRNA variants underwent polyadenylation during maturation. Whereas mutations to the hexanucleotide signal block both polyadenylation and translation, mutations to either the A-rich sequence or the U-rich elements block translation without fully blocking polyadenylation. We conclude that MOS mRNA translation in pig oocytes is subject to a more extensive series of controls than that in lower vertebrates.

3' Untranslated Regions↗