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

Abstract

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...

Local Protein Synthesis Mediates a Rapid Increase in Dendritic Elongation Factor 1A after Induction of Late Long-Term Potentiation

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“…Polyribosomes were purified and analyzed for their ability to translate proteins as described previously (Cosgrove and Rapoport, 1986;Aloni et al, 1992). Briefly, frozen brain specimens from the indicated brain region were placed in buffer A [containing the following (in mM): 320 sucrose, 50 HEPES, 140 potassium acetate, 4 magnesium acetate, 2.5 dithiotheritol, pH 7.5], using a 2.5 vol of buffer A.…”

S6 kinase 1 is required for rapamycin-sensitive liver proliferation after mouse hepatectomy

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