scholarly journals Reproducibility of the Ribosomal RNA Synthesis Ratio in Sputum and Association with Markers of Mycobacterium tuberculosis Burden

2021 ◽  
Author(s):  
Emmanuel Musisi ◽  
Christian Dide-Agossou ◽  
Reem Al Mubarak ◽  
Karen Rossmassler ◽  
Abdul Wahab Ssesolo ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Ribosomal Rna ◽  
Rna Synthesis ◽  
Rrna Synthesis ◽  
Practical Application ◽  
Pharmacodynamic Marker

This study takes a major next step toward practical application of a novel pharmacodynamic marker that we believe will have transformative implications for tuberculosis. This article follows our recent report in Nature Communications that an assay called the rRNA synthesis (RS) ratio indicates the treatment-shortening of drugs and regimens.

scholarly journals REGULATION OF RIBOSOMAL RNA AND 5s RNA SYNTHESIS IN DROSOPHILA MELANOGASTER: I. BOBBED MUTANTS

Genetics ◽  
1972 ◽  
Vol 72 (2) ◽  
pp. 267-276
Author(s):  
Roberto Weinmann
Keyword(s):  
Drosophila Melanogaster ◽  
Developmental Delay ◽  
Ribosomal Rna ◽  
Gel Electrophoresis ◽  
Rna Synthesis ◽  
Rrna Synthesis ◽  
Wild Type ◽  
5S Rna ◽  
Wild Type Level

ABSTRACT Analysis of the rates and amounts of rRNA and 5s RNA synthesized in Drosophila melanogaster bobbed mutants was done by using acrylamide-gel electrophoresis. The results show that the amounts of rRNA synthesized are constant, although the rates of rRNA synthesis in bb's are reduced to 30% of the wild-type level. The rates of synthesis of 5s RNA were constant. The rate of synthesis of the two kinds of molecules that enter in equimolar amounts into the mature ribosome is non-coordinated.—The rates of rRNA synthesis were shown to be proportional to the length of the scutellar bristles, supporting the notion that in trichogen cells there is no developmental delay, but the size of the bristle depends directly on the rate of rRNA synthesis.

scholarly journals GENETIC MODULATION OF RNA METABOLISM IN DROSOPHILA. I. INCREASED RATE OF RIBOSOMAL RNA SYNTHESIS

Genetics ◽  
1977 ◽  
Vol 86 (4) ◽  
pp. 789-800
Author(s):  
Stephen H Clark ◽  
Linda D Strausbaugh ◽  
Barry I Kiefer
Keyword(s):  
Y Chromosome ◽  
Ribosomal Rna ◽  
Development Time ◽  
Rna Synthesis ◽  
Specific Activity ◽  
Rrna Synthesis ◽  
Adult Males ◽  
Wild Type ◽  
Wild Type Phenotype ◽  
Activity Measurements

ABSTRACT It has been suggested that a particular Y chromosome which is rDNA-deficient (YbbSuVar-5) may be associated with an increased utilization of rDNA template in adult testes (Shermoen and Kiefer 1975). To extend the observations on this chromosome, experiments were designed to determine if the chromosome has an effect on rRNA synthesis in bobbed adults and on classic bobbed phenotypes (shortened and thinner scutellar bristles and delayed development). Specific activity measurements were made on rRNA extracted from adult males of the genotypes car bb/Ybb- and car bb/YbbSuVar-5, which are rDNA-deficient to the same extent, and from Samarkand+ isogenic (Sam+ iso), which is a wild-type stock. The resulting data demonstrated that the presence of the YbbSuVar-5 chromosome increases the rate of ribosomal RNA synthesis in adult flies. In addition, it was found that the presence of this particular Y chromosome restores wild-type bristle phenotype and development time. Appropriate genetic crosses indicate that the observed effects (increased rRNA synthesis, restoration of wild-type phenotype) are a function of this particular Y chromosome, and are not due to autosomal factors. The results of these experiments suggest that the rate of rRNA accumulation is under genetic control.

Regulation of ribosomal RNA synthesis in Tetrahymena pyriformis

1978 ◽  
Vol 31 (1) ◽  
pp. 13-23
Author(s):  
J. Keiding ◽  
H.A. Andersen
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Ribosomal Rna ◽  
Rna Synthesis ◽  
Tetrahymena Pyriformis ◽  
Rrna Synthesis ◽  
Constant Rate ◽  
Normal Increase ◽  
S Period ◽  
Dosis Effect

Ribosomal RNA is synthesized at constant rate during most of the cell cycle in heat-shock synchronized populations of Tetrahymena pyriformis. Early in each macronuclear S-period the rate of synthesis increases abruptly, concomitant with replication of the genes coding for ribosomal RNA. The increase is prevented by inhibitors of DNA replication, added prior to the S-period. Similarly, in cultures synchronized by starvation/refeeding, inhibition of DNA replication, at the time when the rDNA is replicated, will prevent the normal increase in rate of RNA synthesis which follows refeeding. We conclude that inhibition of rDNA replication interferes with the synthesis of rRNA, and we suggest that with respect to rRNA synthesis a gene dosis effect is operating in fast-growing Tetrahymena cells.

Cytoplasmic to nuclear translocation of RNA polymerase I is required for lipopolysaccharide-induced nucleolar RNA synthesis and subsequent DNA synthesis in murine B lymphocytes

1989 ◽  
Vol 92 (1) ◽  
pp. 101-109
Author(s):  
M.S. Halleck ◽  
R.A. Schlegel ◽  
K.M. Rose
Keyword(s):  
Rna Polymerase ◽  
Dna Synthesis ◽  
B Lymphocytes ◽  
Ribosomal Rna ◽  
Rna Synthesis ◽  
Nuclear Translocation ◽  
Rna Polymerase I ◽  
Nuclear Accumulation ◽  
Rrna Synthesis ◽  
Polymerase I

The synthesis of ribosomal RNA (rRNA) in murine B lymphocytes is markedly elevated in response to mitogens such as lipopolysaccharide (LPS). First, to investigate the mechanism involved, antibodies directed against RNA polymerase I, the enzyme responsible for transcription of ribosomal genes, were introduced into the cytoplasm of lymphocytes via red cell-mediated microinjection and the ability of cells to synthesize RNA was examined. Simultaneous immunofluorescence/autoradiography revealed that 7% or less of the cells injected with specific antibodies prior to stimulation were actively synthesizing rRNA 15 or 40 h following LPS addition. In contrast 19% and 27% of cells injected with control IgG were active at these times. Non-ribosomal RNA synthesis was unaffected by the presence of anti-RNA polymerase I antibodies. Since antibodies injected into the cytoplasm were limited to that compartment, these data suggest that rRNA synthesis induced by LPS requires translocation of cytoplasmic RNA polymerase I into the nucleus. Second, to test whether synthesis of rRNA is required for entry into S phase, the effect of anti-RNA polymerase I antibodies on DNA synthesis in response to LPS was evaluated. Only 7% of cells containing anti-RNA polymerase I antibodies had initiated DNA synthesis 40 h after LPS addition whereas 25% of cells containing control IgG were actively synthesizing DNA at that time. These results suggest that nuclear accumulation of RNA polymerase I and increased rRNA synthesis are required for LPS-induced DNA synthesis in B lymphocytes.

Inhibition of rRNA synthesis following incorporation of 5-bromodeoxyuridine into DNA of Tetrahymena pyriformis

1975 ◽  
Vol 17 (3) ◽  
pp. 495-502
Author(s):  
A.E. Lykkesfeldt ◽  
H.A. Andersen
Keyword(s):  
Dna Replication ◽  
Ribosomal Rna ◽  
Rna Synthesis ◽  
Nuclear Dna ◽  
Tetrahymena Pyriformis ◽  
Growth Conditions ◽  
Defined Medium ◽  
Rrna Synthesis ◽  
Chemically Defined Medium ◽  
Dividing Cells

Tetrahymena pyriformis was grown on chemically defined medium in the presence of 5-bromodeoxyuridine (BUdR). Under these growth conditions more than 60% of the thymidine sites in DNA were substituted with BUdR. It was found that RNA synthesis was strongly inhibited by the presence of BUdR in DNA. To assure that incorporation of BUdR into DNA was a prerequisite of the effect observed, BUdR was added to synchronously dividing cells. BUdR had no effect on the cells when present outside the period of nuclear DNA replication, whereas RNA synthesis was strongly inhibited as soon as the genes coding for ribosomal RNA had replicated in the presence of BUdR.

scholarly journals Nucleolar necklaces in chick embryo fibroblast cells. II. Microscope observations of the effect of adenosine analogues on nucleolar necklace formation.

1975 ◽  
Vol 65 (2) ◽  
pp. 418-427 ◽  
Author(s):  
D Granick
Keyword(s):  
Chick Embryo ◽  
Ribosomal Rna ◽  
Messenger Rna ◽  
Rna Synthesis ◽  
Rrna Synthesis ◽  
Fibroblast Cells ◽  
Chick Embryo Fibroblast ◽  
Adenosine Analogues ◽  
Nucleolar Apparatus ◽  
Extensive Degradation

The round nucleoli of chick embryo fibroblast cells, when exposed to adenosine (2 mM)or to a number of adenosine analogues, lose material and unravel over a period of several hours to become beaded strands, 20 mu M in length, termed nucleolar necklaces (NN). Light microscope observations on this process are described. Biochemical experiments have revealed that most of these analogues interfere with both messenger RNA synthesis and ribosome synthesis, causing extensive degradation of the preribosome species containing 32S RNA although most of the preribosomes containing 18S RNA survive. We suggest that it is the depletion from the nucleolus of the adhesive 32S and 28S RNA preribosomes which allows the remaining nucleolar apparatus to spread apart into the NN configuration. Also required for the maintenance of the NN structure is the synthesis of some ribosomal RNA (rRNA) possibly present as rRNA "feathers" on the DNA. The addition of inhibitors of rRNA synthesis such as actinomycin D to the NN-containing cells causes loss of rRNA. Then a contraction and collapse of the NN structure into small dense spheres is observed.

scholarly journals Regulation of ribosomal RNA synthesis in T cells: requirement for GTP and Ebp1

Blood ◽  
2015 ◽  
Vol 125 (16) ◽  
pp. 2519-2529 ◽  
Author(s):  
Le Xuan Truong Nguyen ◽  
Yunqin Lee ◽  
Lenore Urbani ◽  
Paul J. Utz ◽  
Anne W. Hamburger ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Ribosomal Rna ◽  
Rna Synthesis ◽  
Binding Protein ◽  
Rrna Synthesis ◽  
T Cell Proliferation ◽  
Gtp Binding ◽  
Key Points

Key Points MPA suppresses ribosomal RNA (rRNA) synthesis and cell proliferation in T cells through TIF-IA, a GTP binding protein. The combination of MPA and sotrastaurin potently suppresses T-cell proliferation and inhibits IL-2 secretion through TIF-IA and ErbB3-binding protein 1 (Ebp1).

scholarly journals Mycobacterium tuberculosis precursor rRNA as a measure of treatment-shortening activity of drugs and regimens

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nicholas D. Walter ◽  
Sarah E. M. Born ◽  
Gregory T. Robertson ◽  
Matthew Reichlen ◽  
Christian Dide-Agossou ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Ribosomal Rna ◽  
Molecular Basis ◽  
Drug Effect ◽  
Human Studies ◽  
Effective Drug ◽  
Fundamental Aspect ◽  
Rrna Synthesis ◽  
Bacterial Burden ◽  
Drug Regimens

AbstractThere is urgent need for new drug regimens that more rapidly cure tuberculosis (TB). Existing TB drugs and regimens vary in treatment-shortening activity, but the molecular basis of these differences is unclear, and no existing assay directly quantifies the ability of a drug or regimen to shorten treatment. Here, we show that drugs historically classified as sterilizing and non-sterilizing have distinct impacts on a fundamental aspect of Mycobacterium tuberculosis physiology: ribosomal RNA (rRNA) synthesis. In culture, in mice, and in human studies, measurement of precursor rRNA reveals that sterilizing drugs and highly effective drug regimens profoundly suppress M. tuberculosis rRNA synthesis, whereas non-sterilizing drugs and weaker regimens do not. The rRNA synthesis ratio provides a readout of drug effect that is orthogonal to traditional measures of bacterial burden. We propose that this metric of drug activity may accelerate the development of shorter TB regimens.

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