Nerve growth factor selectively regulates expression of transcripts encoding ribosomal proteins.

Abstract

BACKGROUND: NGF exerts a variety of actions including promotion of neuronal differentiation and survival. The PC12 rat pheochromocytoma cell line has proved valuable for studying how NGF works and has revealed that the NGF mechanism includes regulation of gene expression. Accordingly, we used SAGE (Serial Analysis of Gene Expression) to compare levels of specific transcripts in PC12 cells before and after long-term NGF exposure. Of the approximately 22,000 transcripts detected and quantified, 4% are NGF-regulated by 6-fold or more. Here, we used database information to identify transcripts in our SAGE libraries that encode ribosomal proteins and have compared the effect of NGF on their relative levels of expression. RESULTS: Among the transcripts detected in our SAGE analysis, 74 were identified as encoding ribosomal proteins. Ribosomal protein transcripts were among the most abundantly expressed and, for naive and NGF-treated PC12 cells, represented 5.2% and 3.5%, respectively, of total transcripts analyzed. Surprisingly, nearly half of ribosomal protein transcripts underwent statistically significant NGF-promoted alterations in relative abundance, with changes of up to 5-fold. Of the changes, approximately 2/3 represented decreases. A time course revealed that the relative abundance of transcripts encoding RPL9 increases within 1 hr of NGF treatment and is maximally elevated by 8 hr. CONCLUSIONS: These data establish that NGF selectively changes expression of ribosomal protein transcripts. These findings raise potential roles for regulation of ribosomal protein transcripts in NGF-promoted withdrawal from the cell cycle and neuronal differentiation and indicate that regulation of individual ribosomal protein transcripts is cell- and stimulus-specific.