Regulation of ribosomal ribonucleic acid levels in growing, 3H-arrested, and crisis-phase WI-38 human diploid fibroblasts

Wolf, Stanley F.; Sameshima, Masazumi; Liebhaber, Steven A.; Schlessinger, David

doi:10.1021/bi00556a012

Cited by 32 publications

(9 citation statements)

References 25 publications

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“…The observation that DNA polymerase CY activity is reduced in aged cells when normalized to protein content reflects increased cell size in these cultures, a phenomenon that has been previously documented (Cristofalo and Kritchevsky, 1969;Mitsui and Schneider, 1976a,b;Schneider and Fowlkes, 1976;Bowman et al, 1975;Wolf et al, 1980). While increased cell size associated with in vitro senescence may be secondary to growth arrest, observations in our laboratory suggest that cell enlargement could be of significance in the onset andor maintenance of the post-mitotic state in senescent cultures.…”

Section: Discussionsupporting

confidence: 76%

Induction of DNA polymerase α in senescent cultures of normal and Werner's syndrome cultured skin fibroblasts

Pendergrass

Saulewicz

Salk

et al. 1985

Journal Cellular Physiology

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DNA polymerase alpha activity was determined following serum stimulation of early and late passages of human diploid fibroblast-like (HDFL) cultures derived from apparently normal donors (two strains) and from a patient with Werner's syndrome (one strain). Induction of this enzyme was observed in both low passage, actively proliferating cultures and in postmitotic "senescent" cultures from all three strains. The maximal polymerase activity of early and late passage cells of each strain were nearly identical when normalized to the number of cells present. However, the activity of the enzyme was observed to be significantly lower in late passage cultures when normalized to total protein content apparently because of enlargement of the senescent cells. The behavior of Werner derived cells was similar to that of the normal cells. The induction of DNA polymerase alpha in senescent cultures indicates that they retain the capacity to carry out some complex metabolic responses to mitogen stimulation. In addition, these results suggest the possibility that dilution of DNA polymerase alpha and/or other DNA replication factors may play a role in the onset or maintenance of the postmitotic state in the enlarged senescent HDFL cells.

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Section: Discussionsupporting

confidence: 76%

Induction of DNA polymerase α in senescent cultures of normal and Werner's syndrome cultured skin fibroblasts

Pendergrass

Saulewicz

Salk

et al. 1985

Journal Cellular Physiology

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“…This mechanism has been observed to operate in resting human lymphocytes, but is eliminated following phytohemaglutinin stimulation (Cooper 1973). Similar results have been observed in resting as compared with serum-stimulated mouse fibroblasts (Johnson et al 1976), in senescent human fibroblasts as compared with proliferating cells (Wolf et al 1980), in embryonic quail myofibres (Bowman and Emerson 1977), and after heat shock of various organisms, including cultured Drosophila cells (Bell et al 1988a) and Xenopus oocytes (Labhart and Reeder 1987).…”

Section: Regulation Of Pre-rrna Processingsupporting

confidence: 74%

Control points in eucaryotic ribosome biogenesis

Larson¹,

Zahradka²,

Sells³

1991

Biochem. Cell Biol.

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Ribosome biogenesis in eucaryotic cells involves the coordinated synthesis of four rRNA species, transcribed by RNA polymerase I (18S, 28S, 5.8S) and RNA polymerase III (5S), and approximately 80 ribosomal proteins translated from mRNAs synthesized by RNA polymerase II. Assembly of the ribosomal subunits in the nucleolus, the site of 45S rRNA precursor gene transcription, requires the movement of 5S rRNA and ribosomal proteins from the nucleoplasm and cytoplasm, respectively, to this structure. To integrate these events and ensure the balanced production of individual ribosomal components, different strategies have been developed by eucaryotic organisms in response to a variety of physiological changes. This review presents an overview of the mechanisms modulating the production of ribosomal precursor molecules and the rate of ribosome biogenesis in various biological systems.

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“…This change is comparable with the two-to threefold increase in cellular content of ribosomes, observed during transitions between resting and growing states of cells in culture (9,33,71), which results from a combination of two or more mechanisms operating in different cell lines and under various growth conditions. These include a decline in the rate of rRNA turnover (1, 19, 48, 77), increase in the rate of its synthesis (26,45), and increase in the rate of its processing (34,79), as well as an increase in the synthesis rate of r-proteins (74).…”

Section: Discussionmentioning

confidence: 99%

Selective translational control and nonspecific posttranscriptional regulation of ribosomal protein gene expression during development and regeneration of rat liver.

Aloni¹,

Peleg²,

Meyuhas³

1992

Mol. Cell. Biol.

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Mammalian liver development is accompanied by a transition from rapid growth in the fetus to a quiescent state in the adult. However, extensive proliferation can be induced in the adult liver by partial hepatectomy. In this study, we examined the regulation of ribosomal protein (rp) gene expression in the developing and regenerating rat liver. Our results indicate that the translation of rp mRNAs is selectively repressed by about 70%o upon development from fetal to adult life, as illustrated by the decrease in ribosomal loading. In addition, the relative abundance of these mRNAs, like that of several other, but not all, housekeeping mRNAs, declines during development through a posttranscriptional mechanism. When liver cells commence growth following partial hepatectomy, translation of rp mRNAs is resumed to near-maximal capacity, as judged by their very efficient recruitment into polysomes. The concomitant increase in the abundance of rp mRNAs under these circumstances is achieved by a posttranscriptional mechanism. The apparent fluctuations in the translation efficiency of rp mRNAs are accompanied by parallel changes in the expression of the genes encoding the initiation factors eIF-4E and eIF-4A. Our results indicate that selective translational control of rp mRNAs in mammals is not confined to manipulated cells in culture but constitutes an important regulatory mechanism operating in vivo in the course of liver development and regeneration.The biosynthesis of ribosomes in vertebrates is primarily coordinated with the cellular growth status and requires an equimolar accumulation of four rRNA and about 80 different ribosomal protein (rp) molecules. This stoichiometry is maintained by coordinate regulation at various levels of gene expression from transcription to protein turnover (4,31,43,49). Clearly, the translational control of rp mRNAs is the most prevalent regulatory mechanism of vertebrate rp gene expression and operates under a variety of physiological conditions (reference 41 and references therein). Recently, we have shown that the 5'-terminal pyrimidine tract, adjacent to the cap site of all vertebrate rp mRNAs rigorously analyzed thus far, plays a critical role in their coordinate translational control (41).Posttranscriptional control of rp genes, most probably through stability of the corresponding transcripts, has been reported to occur in anucleate Xenopus embryos (62) and in dexamethasone-treated rats (21). In addition, control at the RNA processing level is evident for rpL1 in Xenopus laevis (10). Finally, a balanced accumulation of ribosomal proteins (r-proteins) is also achieved by modulating their turnover, as observed in mouse oocytes (39) and differentiating rat myoblasts (30).The development of rodent liver is associated with progressive decrease of mitotic activity to almost undetectable levels in the adult tissue (reference 46 and references therein). Concomitantly, the hepatocytes acquire differentiated functions and lose others. These developmental changes involve extensive alterations...

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Regulation of ribosomal ribonucleic acid levels in growing, 3H-arrested, and crisis-phase WI-38 human diploid fibroblasts

Cited by 32 publications

References 25 publications

Induction of DNA polymerase α in senescent cultures of normal and Werner's syndrome cultured skin fibroblasts

Induction of DNA polymerase α in senescent cultures of normal and Werner's syndrome cultured skin fibroblasts

Control points in eucaryotic ribosome biogenesis

Selective translational control and nonspecific posttranscriptional regulation of ribosomal protein gene expression during development and regeneration of rat liver.

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