Transcription factors induce differential splicing of duplicated ribosomal protein genes during meiosis

Abstract In yeast, most ribosomal proteins are produced from duplicated genes. These nearly identical protein pairs are expressed at varying levels, with one ‘major paralog’ usually predominating. The minor paralog is highly transcribed but held in check through reduced intron removal, but the mechanism and purpose of this copy-specific repression remains unclear. In this study, we searched for proteins that achieve copy-specific expression by acting through the intron of the minor paralog of the model duplicated small ribosomal subunit protein S9 genes. By mass spectrometry and gene deletion we demonstrate that the transcription factors Rim101 and Taf14 bind to the intron and inhibit the splicing of the minor RPS9 paralog. RPS9A is then specifically de-repressed during meiosis to ensure optimal expression of meiotic genes and efficient sporulation. Our results reveal a new regulatory paradigm where transcriptional factors can also modulate splicing rates to optimize the expression of duplicated ribosomal protein genes.