SRA

To better understand the gene regulatory mechanisms that program developmental processes, we carried out simultaneous, genome-wide measurements of mRNA, translation and protein through meiotic differentiation in budding yeast. Surprisingly, we observed that the levels of several hundred mRNAs are anti-correlated with their corresponding protein products. We show that rather than arising from canonical forms of gene regulatory control, the regulation of at least 380 such cases—or over 8% of all measured genes—involves temporally regulated switching between production of a canonical, translatable transcript and a 5'' extended isoform that is not efficiently translated into protein. By this pervasive mechanism for the modulation of protein levels through a natural developmental program, a single transcription factor can coordinately activate and repress protein synthesis for distinct sets of genes. The distinction is not based on whether an mRNA is induced or not, but rather based on the type of transcript produced. Overall design: Sequencing of mRNA molecules and ribosome footprints to identify regulated transcript isoform changes that result in apparent translational regulation. In short,two major experiments are included here, one for parallel mRNA-seq and ribosome profiling of cells progressing through meiosis. This was performed in parallel with mass spectrometry to ascertain the relationship between transcript abundance, translation, and protein abundance over time in a developmental process. The other experiment investigates the effects on transcript abundance and translation of induction of a single transcription factor (Ndt80). The results and analysis of both studies are in the publication, "Pervasive, coordinated protein level changes driven by transcript isoform switching during meiosis" by Ze Cheng*, George Maxwell Otto*, Emily Nicole Powers, Abdurrahman Keskin, Philipp Mertins, Steve Carr, Marko Jovanovic, and Gloria Ann Brar. In press, Cell.