Abstract: The ribosomal protein Rpl12p of Saccharomyces cerevisiae is encoded by duplicated genes, RPL12A and RPL12B. The gene products possess an identical amino acid sequence. Yeast strain 6EA1, which lacks both genes, is viable but exhibits a very slow-growth phenotype. In this study, 6EA1 cells were transformed with plasmids carrying either RPL12A or RPL12B, and the transcriptional profiles of wild-type W303, 6EA1 and the transformed cells grown in synthetic complete medium were examined by microarray analysis. Transcription of PHO84, a gene encoding a high-affinity phosphate transporter, was drastically suppressed in 6EA1. PHO84 expression is induced under phosphate-limiting conditions. Therefore, cells were grown in low-phosphate medium and transcripts encoding the PHO pathway proteins were quantified by qRT-PCR. The high-affinity phosphate transporters and repressible phosphatases were suppressed, while PHO4, a PHO pathway transcription activator, was upregulated in 6EA1. Accordingly, phosphate transport and acidic phosphatase activities were significantly decreased in 6EA1. Addition of RPL12A or RPL12B to 6EA1 largely lessens these effects. We postulate that RPL12 has an extra-ribosomal function in modulating the transcription of genes that need Pho4p activation.