[Age-dependent gene induction in the quail oviduct. Role of post-transcriptional changes in the aging process]

In 1974 we introduced the quail oviduct system to molecular gerontology as a model for investigating age-dependent gene realization at the molecular level. During ageing the amounts of synthesized ovalbumin and avidin, the two major oviduct proteins, decrease to reach almost 0-values. Soon it emerged that the reasons for the reduced ovalbumin and avidin syntheses were not only on the transcriptional but in addition on the posttranscriptional level. It was found that the observed reduced capacity for protein biosynthesis was an age-correlated impairment of those enzyme systems which are involved in the processing of hnRNA to mRNA and in the transport of mRNA from nucleus to cytoplasm. After having firstly discovered and purified some key enzymes of mRNA processing ( endoribonucleases IV, V and VII; U1- snRNP -associated endoribonuclease; poly(A)-specific exoribonuclease ), and secondly studied in detail the enzymically controlled nucleocytoplasmic mRNA transport system, we observed that polyadenylation and perhaps also splicing of hnRNA (two processes in posttranscriptional modification of mRNA) are impaired during ageing. Pronounced changes occur especially at the level of polyadenylation of hnRNA; analytic and enzymic studies revealed that, in parallel with ageing, poly(A) catabolism increases although poly(A) anabolism remains unchanged. The consequences of this change are: reduced stability of mRNA, probably reduced splicing efficiency, reduced binding of mRNA to the inner nuclear membrane or lamina, and reduced nucleocytoplasmic transport of mRNA. The data suggest that changes at the posttranscriptional level are as important in ageing as changes in transcription, and they may explain the observed, age-dependent reduction of the amount of functional mRNA in the cytoplasm.