IDENTIFICATION OF A TRANSCRIPT THAT IS DOWN-REGULATED IN SENESCENT HUMAN FIBROBLASTS - CLONING, SEQUENCE-ANALYSIS, AND REGULATION OF THE HUMAN L7 RIBOSOMAL-PROTEIN GENE

Normal eukaryotic cells divide only a limited number of times before p roliferation ceases due to cellular senescence. We previously reported that a constitutively expressed, non-cell cycle-regulated transcript of unknown identity declines severalfold when human fibroblasts become senescent. We show here, from the sequence of cDNA and genomic clones , that this transcript encodes L7, a structural protein of the large r ibosomal subunit. The human L7 protein shares > 90% amino acid identit y with the mouse and rat L7 proteins but is shorter than either rodent protein due to fewer basic repetitive motifs at the amino terminus. T he position of the first intron is conserved between the mouse and hum an genes. The L7 mRNA was abundant, stable (t1/2 > 10 h), and polyaden ylated in presenescent and senescent human fibroblasts; however, stead y state mRNA levels were 5-10-fold lower in senescent cells, whether d erived from fetal lung or neonatal foreskin. Quiescent and senescent c ells synthesized protein at similar rates, yet only senescent cultures showed a decline in L7 mRNA. The mRNAs encoding five other ribosomal proteins (L5, P1, S3, S6, and S10) behaved similarly. The results sugg est that the senescence-associated decline in L7 and other ribosomal p rotein mRNAs is unrelated to growth state or protein synthetic rate pe r se and support the view that senescence and quiescence are dissimila r states.