Increased Expression of the S25 Ribosomal Protein Gene Occurs during Ageing of the Rat Liver

Abstract

Background: It appears that consistent changes in the levels of activity of a small cohort of genes (probably <1% of all active genes) occur in all mammalian cells during ageing. Identification of such genes could provide valuable insights into the ageing process. Objective: We have studied age-related changes in gene expression profiles in the rat liver. One of the genes which exhibited clear and consistent increases in expression is characterised. Methods: Analysis of the gene expression profile was carried out using a combination of an optimised form of differential display and single-strand conformational polymorphism (SSCP) gel analysis. Gene expression levels were quantified by Northern blot analysis. The gene’s identity was determined by comparing its nucleotide sequence to DNA databases. Results: During this investigation we observed one gene which exhibited an increase in expression in livers from young adult (6 months) to old adult (24 months) rats. The differential expression of this gene was confirmed by SSCP gel analysis and Northern blotting. Densitometry of the latter indicated that expression increased by 165% with age. Characterisation of the isolated polymerase chain reaction fragment demonstrated it to code for the ribosomal protein S25 (RPS25). Conclusion: This increase in RPS25 expression is further evidence that the composition of ribosomes may alter with age and as a result could have significant effects on protein synthesis.

Structural basis for the binding of IRES RNAs to the head of the ribosomal 40S subunit

“…The data coincide with previous biochemical results performed in the presence of CrPV and HCV IRES (40). Interestingly, the transcription of the rpS25 mRNA is increased several fold in mammalian and human cells under stress conditions like amino acid starvation or apoptosis (68,69). It is conceivable that a free pool of rpS25 might block the attachment of IRES structures to 40S subunits and thus protects the cell of translation of unfavourable mRNAs.…”

RPS25 is essential for translation initiation by the Dicistroviridae and hepatitis C viral IRESs

“…In mammalian cells, Rps25 expression appears to be regulated both spatially and temporally. Rps25 mRNA is increased to 165% of regular levels in aging rat livers (Lavery and Goyns 2002), and is increased almost sixfold during amino acid starvation in rat FAO hepatoma cells (Laine et al 1994). A 2.1-fold decrease in RPS25 mRNA abundance occurs in rat PC12 pheochromocytoma cells that have been treated with nerve growth factor (Angelastro et al 2002).…”

Aging and innate immune cells

“…The C4BP␤ subunit interacts with the coagulation cascade, whereas C4BP␣ specifically binds to C4b and inhibits complement activation [140]. Using a rat model, Lavery and Goyns [141] described a decrease in the expression of the C4BP␣ in the livers of aged animals; however, it is unknown whether this observation is organ-or species-specific.…”