Regulation of ribosomal protein genes: An ordered anarchy.

Ribosomal protein genes are among the most highly expressed genes in most cell types. Their products are generally essential for ribosome synthesis, which is the cornerstone for cell growth and proliferation. Many cellular resources are dedicated to producing ribosomal proteins and thus this process needs to be regulated in ways that carefully balance the supply of nascent ribosomal proteins with the demand for new ribosomes. Ribosomal protein genes have classically been viewed as a uniform interconnected regulon regulated in eukaryotic cells by target of rapamycin and protein kinase A pathway in response to changes in growth conditions and/or cellular status. However, recent literature depicts a more complex picture in which the amount of ribosomal proteins produced varies between genes in response to two overlapping regulatory circuits. The first includes the classical general ribosome-producing program and the second is a gene-specific feature responsible for fine-tuning the amount of ribosomal proteins produced from each individual ribosomal gene. Unlike the general pathway that is mainly controlled at the level of transcription and translation, this specific regulation of ribosomal protein genes is largely achieved through changes in pre-mRNA splicing efficiency and mRNA stability. By combining general and specific regulation, the cell can coordinate ribosome production, while allowing functional specialization and diversity. Here we review the many ways ribosomal protein genes are regulated, with special focus on the emerging role of posttranscriptional regulatory events in fine-tuning the expression of ribosomal protein genes and its role in controlling the potential variation in ribosome functions. This article is categorized under: Translation > Ribosome Biogenesis Translation > Ribosome Structure/Function Translation > Translation Regulation.

Introns regulate the production of ribosomal proteins by modulating splicing of duplicated ribosomal protein genes.

Most budding yeast introns exist in the many duplicated ribosomal protein genes (RPGs) and it has been posited that they remain there to modulate the expression of RPGs and cell growth in response to stress. However, the mechanism by which introns regulate the expression of RPGs and their impact on the synthesis of ribosomal proteins remain unclear. In this study, we show that introns determine the ratio of ribosomal protein isoforms through asymmetric paralog-specific regulation of splicing. Exchanging the introns and 3' untranslated regions of the duplicated RPS9 genes altered the splicing efficiency and changed the ratio of the ribosomal protein isoforms. Mutational analysis of the RPS9 genes indicated that splicing is regulated by variations in the intron structure and the 3' untranslated region. Together these data suggest that preferential splicing of duplicated RPGs provides a means for adjusting the ratio of different ribosomal protein isoforms, while maintaining the overall expression level of each ribosomal protein.