Regulation of tyrosine aminotransferase messenger ribonucleic acid in rat liver. Effect of cycloheximide on messenger ribonucleic acid turnover

Ernest, Michael J.

doi:10.1021/bi00269a022

Cited by 41 publications

(16 citation statements)

References 29 publications

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“…This observation confirms an earlier work, in which the effects of polysome stabilizing and destabilizing inhibitors were compared (22~ The stimulatory effect of emetin but not of p'actamycin adds to their list of inhibitors showing this correlation, and supports their hypothesis that tRNA synthesis may be regulated by a factor, whose effective concentration is determined by an equilibrium between a free and a polysome bound form. A stimulatory effect ofpuromycin on tRNA synthesis observed by WILLIS et al (24) does not necessarily contradict this theory, since the premature chain termination induced by puromycin not always leads to a disaggregation ofpolysomes (10). The 50 to 60% stimulation oftRNA synthesis observed in the present experiments is calculated to represent about 27,000 molecules per cell, or a stimulation of about 600 tRNA molecules per min.…”

Section: Discussionsupporting

confidence: 54%

The cytoplasmic accumulation of non-polyadenylated RNA in rat thymocytes is differentially changed at an early time of protein synthesis inhibition

Engelhardt

1984

Carlsberg Res. Commun.

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The cytoplasmic accumulation of newly synthesized RNA in rat thymocytes has been analyzed during the first 45 min of protein synthesis inhibition by cycloheximide, emetin, puromycin or pactamycin. Electrophoretic fractionation of double labelled RNA showed no changes in the isotope ratio of single fractions of poly(A)'-RNA within an experimental error corresponding to +2 to +20 molecules per ceil. In poly(A)--RNA, two types of changes were induced. All four inhibitors stimulated the incorporation in presumptive histone mRNA and inhibited the accumulation of 18 S rRNA. A stimulated accumulation of tRNA was induced only by cycloheximide and emetin, two polysome stabilizing compounds. Labelling of 28 S rRNA was only slightly affected, except in the presence ofcycloheximide, where it increased more than twofold. This suggests that cycloheximide may induce an accelerated nuclear-cytoplasmic transfer of 28 S rRNA. The changes induced in poly(A)--RNA are thus either inhibitor specific, or a result of a sensitivity to protein synthesis per se.

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Section: Discussionsupporting

confidence: 54%

The cytoplasmic accumulation of non-polyadenylated RNA in rat thymocytes is differentially changed at an early time of protein synthesis inhibition

Engelhardt

1984

Carlsberg Res. Commun.

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“…We have analyzed the poly(A) size distribution of four liver mRNAs of various stabilities. While both SAA and ALB mRNA could be considered as stable [half-life Ͼ 24 hr (24,35)], TAT and PCK are unstable [half-life between 30 min and 2 hr (36,37)]. Decapped species were detected for all these mRNAs and they always have a shorter poly(A) tail than their capped counterparts, suggesting the generality of the deadenylylationdependent decapping pathway irrespective of the stability of the mRNA [as observed in yeast (6)].…”

Section: Traces Of Decapped Species With a Short Poly(a) Tail Can Be mentioning

confidence: 96%

Messenger RNA deadenylylation precedes decapping in mammalian cells

Couttet

Fromont‐Racine

Steel

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

197

191

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In yeast, the major mRNA degradation pathway is initiated by poly(A) tail shortening that triggers mRNA decapping. The mRNA is then degraded by 5-to-3 exonucleolysis. In mammalian cells, even though poly(A) tail shortening also precedes mRNA degradation, the degradation pathway has not been elucidated. We have used a reverse transcription-PCR approach that relies on mRNA circularization to measure the poly(A) tail length of four mammalian mRNAs. This approach allows for the simultaneous analysis of the 5 and 3 ends of the same mRNA molecule. For all four mRNAs analyzed, this strategy permitted us to demonstrate the existence of small amounts of decapped mRNA species which have a shorter poly(A) tail than their capped counterparts. Kinetic analysis of one of these mRNAs indicates that the decapped species with a short poly(A) tail are mRNA degradation products. Therefore, our results indicate that decapping is preceded by a shortening of the poly(A) tail in mammalian cells, as it is in yeast, suggesting that this mRNA degradation pathway is conserved throughout eukaryotic evolution.Messenger RNA degradation contributes significantly to the regulation of gene expression. In eukaryotes, elucidation of a number of mRNA degradation pathways is under way (for reviews, see refs 1-4). Presently, these pathways are better understood in yeast than in mammalian cells. Both in yeast and in mammalian cells, degradation of most polyadenylylated mRNAs appears to be initiated by poly(A) shortening: transcriptional pulse-chase experiments have shown that shortening of the poly(A) tail precedes mRNA degradation (5, 6). Some regulatory sequence determinants affect mRNA stability by modulating the rate of deadenylylation, whereas others modulate a later degradation step (5-7). This later step has been elucidated in yeast: deadenylylation at the 3Ј end triggers mRNA decapping at the 5Ј end, which is then followed by 5Ј-to-3Ј exonucleolysis (refs. 8 and 9 and references therein). In some specific circumstances, other degradation pathways are observed: exonucleolysis from the 3Ј end can occur when the 5Ј-to-3Ј exonuclease is inactive, and a decapping pathway independent of poly(A) tail shortening is involved in the degradation of mRNAs that show premature translation termination (9-11).In mammalian cells, the degradation pathway that follows deadenylylation is not well understood. Uncapped mRNAs are less stable than their capped counterparts in cell extracts, and enzymatic activities that catalyze mRNA decapping and 5Ј-to-3Ј exonucleolysis have been identified (refs. 1 and 3 and references therein). Furthermore, there is a conservation between yeast and mammalian cells of a functional interaction between the 5Ј and 3Ј ends of mRNAs: in both systems, these two ends contribute to translational control (e.g., see refs. 12 and 13). It is thus tempting to speculate that deadenylylation triggers a decapping-dependent degradation pathway in mammalian cells as well. However, a direct demonstration is lacking.We have developed a revers...

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“…A link between translation and RNA degradation has been shown in numerous instances, notably through the inhibition of mRNA decay by cycloheximide (35)(36)(37). In the case of early immediate transcripts with AU-rich elements, like c-myc and c-fos mRNA, degradation is preceded by poly(A)-tail shortening (38).…”

Section: Fig 6 Effect Of Different Rna Synthesis Inhibitors On Tfr mentioning

confidence: 99%

Effect of Transcription Inhibitors on the Iron-dependent Degradation of Transferrin Receptor mRNA

Seiser

Posch

Thompson³

et al. 1995

Journal of Biological Chemistry

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Transferrin receptor (TfR) mRNA expression is tightly linked to intracellular iron levels. Upon iron deprivation, the iron regulatory protein (IRP) stabilizes TfR mRNA by binding to stem-loop structures in its 3-untranslated region, whereas increased iron levels result in inactivation of the mRNA-binding protein and rapid degradation of TfR mRNA. Although IRP and the regulation of its RNA binding activity have been studied intensively, little is known about the mechanism of TfR mRNA degradation. In order to get more information about factors involved in this process we investigated the in vivo IRP-RNA interaction and the effect of transcription inhibitors on the iron-dependent decay of TfR mRNA. Here we demonstrate that part of the active IRP co-localizes with TfR mRNA to the rough endoplasmic reticulum. High intracellular iron levels led to a drastic reduction of this active RNA-bound IRP in vivo, indicating that IRP dissociates prior to TfR mRNA decay. Furthermore, the transcription inhibitor actinomycin D and translation inhibitor cycloheximide suppressed TfR mRNA degradation but did not interfere with the IRP dissociation step. Other inhibitors of RNA polymerase II had no effect on iron-dependent degradation of TfR mRNA. However, high concentrations of ␣-amanitin known to block transcription by RNA polymerase III interfered with mRNA decay suggesting the involvement of polymerase III transcripts in the degradation pathway.

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Regulation of tyrosine aminotransferase messenger ribonucleic acid in rat liver. Effect of cycloheximide on messenger ribonucleic acid turnover

Cited by 41 publications

References 29 publications

The cytoplasmic accumulation of non-polyadenylated RNA in rat thymocytes is differentially changed at an early time of protein synthesis inhibition

The cytoplasmic accumulation of non-polyadenylated RNA in rat thymocytes is differentially changed at an early time of protein synthesis inhibition

Messenger RNA deadenylylation precedes decapping in mammalian cells

Effect of Transcription Inhibitors on the Iron-dependent Degradation of Transferrin Receptor mRNA

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