Journal ArticleDOI
Inhibition of RNA synthesis by actinomycin D: characteristic dose-response of different RNA species.
Robert P. Perry,Dawn E. Kelley +1 more
TLDR
Over the range of actinomycin concentrations employed cellular uptake of the drug is proportional to external concentration, and maximal inhibition of RNA synthesis is generally achieved within one hour after exposure.Abstract:
A quantitative dose-response study was made of the inhibition by actinomycin D of the synthesis of various RNA species in cultured L cells. After a suitable preincubation with various concentrations of actinomycin, synthesis was measured by a brief incorporation of radioactive uridine. The 45S precursor of ribosomal RNA, 5S ribosomal RNA, transfer RNA and various sized fractions of heterogeneous nuclear RNA were extracted from the appropriate subcellular fractions and resolved by acrylamide gel electrophoresis. Polyribosomal messenger RNA was also studied. Over the range of actinomycin concentrations employed cellular uptake of the drug is proportional to external concentration, and maximal inhibition of RNA synthesis is generally achieved within one hour after exposure.
For most of the RNA species studied the dose-response data appear to follow an exponential inactivation function with some “tailing” evident at the higher doses. Sensitivities, defined as the reciprocal of the dose necessary to reduce synthesis to 1/e of the control level, were compared and examined with respect to the molecular weight of the RNA species under consideration. Among the heterogeneous nuclear RNA's there is a good correlation between RNA size and sensitivity, such that the sensitivity per unit molecular weight is relatively constant. A similar relationship is roughly applicable to the ribosomal and transfer RNA's when taken as a group, although in this case the sensitivity per unit molecular weight is 50 to 100 fold greater.
A model is proposed in which this marked difference in actinomycin sensitivity arises as a consequence of the transcription of stretches of contiguous repetitive genes by RNA polymerase molecules which attach to the DNA only at a limited number of entry points, the highest probability of attachment being at the beginning of a stretch.read more
Citations
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Journal ArticleDOI
Nucleolar proteome dynamics
Jens S. Andersen,Yun Wah Lam,Anthony K.L. Leung,Shao En Ong,Carol E. Lyon,Angus I. Lamond,Matthias Mann +6 more
TL;DR: The data establish a quantitative proteomic approach for the temporal characterization of protein flux through cellular organelles and demonstrate that the nucleolar proteome changes significantly over time in response to changes in cellular growth conditions.
Journal ArticleDOI
Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm
TL;DR: It is shown here that several of the abundant hnRNP proteins, including Al, shuttle between the nucleus and the cytoplasm, and may thus also have cy toplasmic functions.
Journal ArticleDOI
Regulation of HDM2 activity by the ribosomal protein L11
TL;DR: In this article, the ribosomal protein L11 can interact with HDM2 and inhibit its function, thus leading to the stabilization and activation of p53 in response to perturbations in ribosome biogenesis.
Journal ArticleDOI
Remodeling of the Enhancer Landscape during Macrophage Activation Is Coupled to Enhancer Transcription
Minna U. Kaikkonen,Nathanael J. Spann,Sven Heinz,Casey E. Romanoski,Karmel A. Allison,Joshua D. Stender,Hyun B. Chun,David F. Tough,Rab K. Prinjha,Christopher Benner,Christopher K. Glass +10 more
TL;DR: An essential role of enhancer transcription in H3K4me1/2 deposition at de novo enhancers that is independent of potential functions of the resulting eRNA transcripts is suggested.
Journal ArticleDOI
Ribosomal protein L11 negatively regulates oncoprotein MDM2 and mediates a p53-dependent ribosomal-stress checkpoint pathway.
Yanping Zhang,Gabrielle White Wolf,Krishna P. Bhat,Aiwen Jin,Theresa Allio,William A. Burkhart,Yue Xiong +6 more
TL;DR: It is shown that the functional consequence of L11-HDM2 association results in the prevention of HDM2-mediated p53 ubiquitination and degradation, subsequently restoring p53-mediated transactivation, accumulating p21 protein levels, and inducing a p 53-dependent cell cycle arrest by canceling the inhibitory function of HDm2.
References
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Journal ArticleDOI
Visualization of Nucleolar Genes
O. L. Miller,Barbara R. Beatty +1 more
TL;DR: The presence of extrachromosomal nucleoli in amphibian oocytes has permitted isolation and electron microscopic observation of the genes coding for ribosomal RNA precursor molecules.
Journal ArticleDOI
Studies of the binding of actinomycin and related compounds to DNA
Werner Müller,Donald M. Crothers +1 more
TL;DR: The physical property which distinguishes actinomycin from the simpler analogs (which lack biological activity) is a very slow dissociation reaction, several orders of magnitude slower than for the non-active analogs.
Journal ArticleDOI
Electrophoretic separation of viral nucleic acids on polyacrylamide gels
TL;DR: The elution of viral RNA from gel slices and the demonstration of infectivity after electrophoresis are described, showing a general relationship between the logarithm of the molecular weight and the relative electrophoretic mobility.
Book
The radiobiology of cultured mammalian cells
TL;DR: The radiobiology of cultured mammalian cells is one book that the authors really recommend you to read, to get more solutions in solving this problem.
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