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Results for “RNA Regulation”

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At least 127 records · Page 7Linked to original sources
PubMed1994

Enhancer 1 binding factor (E1BF), a Ku-related protein, is a growth-regulated RNA polymerase I transcription factor: association of a repressor activity with purified E1BF from serum-deprived cells.

Previous studies from this laboratory have demonstrated that the enhancer 1 binding factor (E1BF), a Ku-related protein, purified from the serum-enriched cells functions as a positive factor in an RNA polymerase (pol I) transcription system. We have now shown that E1BF purified from the serum-deprived cells (E1BFs) can inhibit rDNA transcription completely in a fractionated extract from the cells grown in serum-enriched medium. The suppression of transcription was overcome by the addition of control E1BF (E1BFc). Immunoprecipitation of purified E1BFs by the anti-Ku monoclonal antibody and addition of the supernatant to the transcription reaction mixture prevented the inhibition significantly, whereas immunoprecipitation with the control mouse IgG did not restore the transcription. The transcriptional repressor activity associated with the final DNA affinity column fractions copurified with E1BF. Neither the amount of E1BF nor its promoter binding activity was altered following serum depletion. E1BFs selectively inhibited the initiation of rDNA transcription. The inhibitory activity of E1BFs was not due to a nonspecific RNase activity. These data suggest that E1BF is post-translationally modified following serum starvation of cells, and that the repressor activity of E1BFs is largely responsible for the down-regulation of pol I transcription in serum-deprived cells.

Animals↗
PubMed2026

Maternal PAN2 selectively maintains mRNA Poly(A) tail homeostasis to regulate RNA degradation during oocyte-to-early embryo transition in mice.

In mammals, the precise degradation of maternal mRNAs is essential for oocyte maturation and early embryonic development, as it facilitates the "maternal-to-zygotic transition (MZT)" by eliminating maternal transcripts and enabling zygotic genome activation (ZGA). However, the physiological role of the poly(A)-specific nuclease 2 (PAN2), a deadenylase that initiates cascade degradation of long-tailed transcripts, remains unknown. Here, we generated oocyte-specific Pan2 conditional knockout (cKO) mice to investigate its role. We found that Pan2 cKO females exhibit severe female subfertility despite normal oocyte maturation and ovulation, with embryos arresting at the 2-cell stage. PAIso-seq2 and transcriptome sequencing reveal that PAN2 coordinates maternal mRNA deadenylation and decay. Mechanistically, PAN2 recognizes its substrates through a PAN3-PABPC1 bridging complex, and it preferentially targets transcripts whose poly(A) tails lack guanosine (G) but are enriched for uridine (U). PAN2 deficiency causes poly(A) tail dyshomeostasis, leading to global accumulation of maternal mRNAs, impaired zygotic genome activation, and abnormal protein accumulation in 2-cell embryos. Overexpression of these proteins phenocopies developmental defects. Notably, the PAN2-regulated transcriptome is largely non-overlapping with the LC3B-mediated degradation pathway, highlighting the unique and non-redundant role of PAN2 in maternal mRNA clearance. Our study establishes maternal PAN2 as a critical regulator of poly(A) tail homeostasis, ensuring timely maternal mRNA clearance and proper ZGA, highlighting the stage-specific and tail-composition-dependent functions of the deadenylase cascade during the maternal-to-zygotic transition. These findings offer new perspectives on post-transcriptional regulatory mechanisms in early mammalian embryogenesis.

Deadenylation↗
PubMed1983

Messenger RNA regulation during compensatory renal growth.

The normal pattern of mRNA metabolism almost certainly becomes altered after uninephrectomy, especially during the first day when ribosomes accumulate in the proximal tubular cells of the remaining kidney. For example, within the first hour after nephrectomy, the fraction of newly synthesized poly(A)-deficient mRNA increases relative to poly(A)-containing mRNA. Investigation of other growth-specific regulatory changes in renal mRNA has been complicated by its heterogeneity with respect to translational activity, polyadenylate content, membrane association, and cytoplasmic distribution. In general, analysis of kidney mRNA metabolism during growth has not been sufficiently thorough in that few timepoints have been examined after nephrectomy and the techniques used have been suited primarily to the study of only abundant mRNA sequences. Application of recombinant DNA methods should eliminate these difficulties and permit quantitative measurement of growth-specific genetic events during compensatory growth of the kidney.

Animals↗
PubMed1999

A conformational switch at the 3' end of a plant virus RNA regulates viral replication.

3' untranslated regions of alfamo- and ilar-virus RNAs fold into a series of stem-loop structures to which the coat protein binds with high affinity. This binding plays a role in initiation of infection ('genome activation') and has been thought to substitute for a tRNA-like structure that is found at the 3' termini of related plant viruses. We propose the existence of an alternative conformation of the 3' ends of alfamo- and ilar-virus RNAs, including a pseudoknot. Based on (i) phylogenetic comparisons, (ii) in vivo and in vitro functional analyses of mutants in which the pseudoknot has been disrupted or restored by compensatory mutations, (iii) competition experiments between coat protein and viral replicase, and (iv) investigation of the effect of magnesium, we demonstrate that this pseudoknot is required for replication of alfalfa mosaic virus. This conformation resembles the tRNA-like structure of the related bromo- and cucumo-viruses. A low but specific interaction with yeast CCA-adding enzyme was found. The existence of two mutually exclusive conformations for the 3' termini of alfamo- and ilar-virus RNAs could enable the virus to switch from translation to replication and vice versa. The role of coat protein in this modulation and in genome activation is discussed.

3' Untranslated Regions↗
PubMed1982

Posttranslationally modified ornithine decarboxylase may regulate RNA polymerase I activity.

Purified ornithine decarboxylase (EC 4.1.1.17, ODC) transamidated with four putrescine moieties on four glutamine residues through the action of transglutaminase (EC 2.3.2.13, TGase) purified from guinea pig liver, when added to isolated rat liver nuclei, stoichiometrically increased the activity of RNA polymerase I (EC 2.7.7.6). The increase was relative to the pmoles of purified conjugated ODC added to the reaction and could be reinitiated after the reaction had plateaued by the further addition of ODC-putrescine conjugate. The kinetics of the reaction suggest that the ODC-putrescine conjugate was not reused but degraded after each initiation. Otherwise, the rapid plateau would not be observed. The repeated addition of 278 pmoles of purified ODC-putrescine conjugate to rat liver nuclear preparations containing 200 micrograms total protein consistently stimulated the incorporation of 600-700 pmoles UMP/mg protein. We suggest that ODC transamidated by its product putrescine may be the posttranslationally modified 65,000 Mr protein which has been reported by several laboratories to serve as a labile subunit of RNA polymerase I.

Animals↗
PubMed1984

Glucocorticoid-mediated induction of alpha 1-acid glycoprotein: evidence for hormone-regulated RNA processing.

We have studied the glucocorticoid-mediated accumulation of alpha 1-acid glycoprotein (AGP) in mRNA in HTC rat hepatoma cells. In contrast to the well-characterized primary response of mouse mammary tumor virus, in vitro transcription assays in isolated nuclei show that the rate of transcription of the AGP gene is high even in the absence of hormone. Despite the constitutive transcription of the AGP gene, no detectable AGP RNA can be found in either the cytoplasm or the nuclei of untreated cells. Previous experiments have shown that the glucocorticoid induction of AGP RNA requires ongoing protein synthesis. In conjunction with the present study, our data suggest that glucocorticoids stimulate accumulation of AGP RNA by inducing an RNA processing factor that allows production of stable transcripts.

Animals↗
PubMed1991

A regulated RNA binding protein also possesses aconitase activity.

A clone for the iron-responsive element (IRE)-binding protein (IRE-BP) has been transfected and expressed in mouse fibroblasts. The IRE-BP gene product binds IREs with high affinity and specificity. Amino acid alignments reveal that the IRE-BP is 30% identical to mitochondrial aconitase. The 18 active site residues of mitochondrial aconitase are identical to those in the IRE-BP, suggesting that the IRE-BP may possess aconitase activity. After purification of native IRE-BP and immunoaffinity purification of transfected and expressed IRE-BP, we demonstrate that the purified IRE-BP has aconitase activity.

Aconitate Hydratase↗
PubMed1997

Sequence requirements for regulated RNA splicing of the human fibroblast growth factor receptor-1 alpha exon.

Progression of astrocytes from a benign to a malignant phenotype is accompanied by a change in the RNA processing of the fibroblast growth factor receptor 1 (FGFR-1) gene. The level of a high affinity form of the FGFR-1 is dramatically elevated as a result of alpha-exon skipping during RNA splicing. In this paper we have been able to duplicate this tumor-specific RNA processing pathway by transfection of a chimeric minigene containing a 4-kilobase fragment of the human FGFR-1 gene (including the alpha-exon) into a variety of cell lines. In a transfected human astrocytoma cell line, alpha-exon skipping was consistently observed for RNA transcripts derived from both the chimeric minigene and endogenous gene expression. This exon skipping phenotype was dependent on the size of the flanking intron as deletions which reduced the introns to less than approximately 350 base pairs resulted in enhanced alpha-exon inclusion. Increased exon inclusion was not sequence-specific as exon skipping could be restored with insertion of nonspecific sequence. Cell-specific exon recognition was maintained with a 375-nucleotide sequence inclusive and flanking the alpha-exon, provided that intron size was maintained. These results identify the minimal cis-regulatory sequence requirements for exclusion of FGFR-1 alpha-exon in astrocytomas.

Base Sequence↗
PubMed2000

Flagellum ontogeny in trypanosomes studied via an inherited and regulated RNA interference system.

The African trypanosome, Trypanosoma brucei possesses a large and unique intraflagellar structure called the paraflagellar rod (PFR). The PFR is composed of 2 major proteins, PFRA and PFRC. We have generated an inducible mutant trypanosome cell line (snl-2) that expresses linked inverted copies of a PFRA gene, capable of forming a PFRA double-stranded (ds) RNA. When expression of this dsRNA was induced, new PFRA RNA and PFRA protein quickly disappeared and PFR construction was affected, resulting in cell paralysis. This inducible RNA interference (RNAi) effect was fast-acting, heritable and reversible. It allowed us to demonstrate that PFR proteins are able to enter both mature and growing flagella but appear to concentrate differentially in new flagella because of the construction process. The PFR is constructed by a polar assembly process at the distal end of the flagellum resulting in a stable cytoskeletal structure with low turn-over. The inducible RNAi approach will have widespread applicability in studies of gene function and cellular processes in parasites.

Animals↗
PubMed1982

[Analysis of soluble nuclear fractions regulating RNA synthesis].

The influence of the rat liver nuclear extract on RNA synthesis in the system of isolated cell nuclei of the rat liver was investigated. Two factors were discovered with opposite influence on RNA synthesis: one stimulating, while the other inhibiting the synthesis. A fraction of high-polymeric RNA (7-9 S) and a fraction of the total protein were isolated from the extract. The influence of these fractions on the transcription process was studied both in isolated nuclei and in the system containing pure liver DNA in the presence of RNA polymerase of E. coli. In both the cases the total fraction of protein turned out to stimulate RNA synthesis, while the high-polymeric fraction of RNA inhibited it. The soluble fractions, detected in the cells and influencing RNA synthesis, interact with RNA polymerase either increasing or decreasing the activity of the enzyme.

Animals↗
PubMed1995

Gene regulation by antisense RNA in the fission yeast Schizosaccharomyces pombe.

This report describes experiments designed to demonstrate the suitability of the fission yeast Schizosaccharomyces pombe as a host for antisense RNA regulation. A lacZ gene-expressing yeast strain was constructed and used as a host for the expression of a series of antisense RNAs complementary to various regions of the target lacZ mRNA. All lacZ antisense genes were placed under control of the thiamine-repressible nmt1 promoter of S. pombe and expressed from episomal plasmids. For each antisense plasmid a corresponding sense control plasmid was constructed. All lacZ antisense genes were shown to express antisense RNAs of the expected size at equivalent steady-state levels. beta-Galactosidase activity in transformed cells expressing the long, short 5' or short 3' lacZ antisense RNAs was shown to be reduced by 45%, 20%, and 10%, respectively, relative to control transformants. Further experiments indicated that antisense RNA regulation in this system was conditional and reversible, with the observed reduction of beta-galactosidase activity being dependent on the transcription of lacZ antisense RNA. Our results represent the first successful example of antisense RNA regulation of gene expression in yeast and establish S. pombe as an experimental model for the biochemical analysis of antisense RNA regulation.

Base Sequence↗
PubMed1988

Two forms of RPO41-dependent RNA polymerase. Regulation of the RNA polymerase by glucose repression may control yeast mitochondrial gene expression.

We have identified two chromatographically separable forms of mitochondrial RNA polymerase from Saccharomyces cerevisiae which utilize different DNA templates. One form is only active in a nonselective assay utilizing a poly[d(A-T)] template. The other form selectively initiates from a mitochondrial promoter consensus sequence. Both enzymes can be extracted from yeast mitochondria and all components are encoded by nuclear genes. The possibility that these two activities represent core and holoenzyme forms of the multicomponent mitochondrial RNA polymerase is supported by our observation that both enzymes are absent from a strain bearing a disrupted copy of the RPO41 gene (Greenleaf, A. L., Kelly, J. L., and Lehman, I. R. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 3391-3399). The two enzyme activities are differentially regulated by carbon source; the nonselective enzyme is repressed during growth on glucose relative to the selective enzyme. The 5-fold increase in RNA polymerase activity on a nonrepressing carbon source correlates with the increased level of transcript production from mitochondrial DNA. These results suggest that the mitochondrial RNA polymerase and, in consequence, mitochondrial transcription are regulated by carbon catabolite control.

Chromatography↗