Senescent human fibroblasts have a post-transcriptional block in the expression of the proliferating cell nuclear antigen gene.
The product of the proliferating cell nuclear antigen (PCNA) gene is the co-factor of DNA polymerase delta, which is required for cellular and viral DNA replication. Its steady-state mRNA levels are growth-regulated in young human diploid fibroblasts (HDF) as well as in many other cell types. In senescent HDF, PCNA mRNA is not detectable. However, the PCNA gene is transcribed in senescent HDF as efficiently as in young cells. Furthermore, PCNA hnRNA is easily detectable by reverse transcriptase-polymerase chain reaction in both senescent and young HDF, and the levels are essentially similar. These results indicate that in senescent HDF which are incapable of synthesizing cellular DNA, one of the genes coding for a protein of the DNA-synthesizing apparatus is still transcribed, but the product fails to be processed into mature mRNA.
Department of Pathology, Temple University Medical School, Philadelphia, Pennsylvania 19140.
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CD
Chang
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Phillips
K E
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Lipson
V J
VJ
Cristofalo
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Baserga
D002453:Cell Cycle; D002470:Cell Survival; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018809:Proliferating Cell Nuclear Antigen; D012323:RNA Processing, Post-Transcriptional; D012332:RNA, Heterogeneous Nuclear / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D006133:Growth Substances; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D012332:RNA, Heterogeneous Nuclear; D012333:RNA, Messenger