REGEXTRA · A Novel Level for the Regulation of Eukaryotic Gene Expression: Coupling Transcription to Translation

Eukaryotic gene expression is a highly regulated, fundamental cellular process encompassing distinct steps such as transcription, mRNA processing and nuclear export, translation and degradation of the mRNA. In this project a novel level in the regulation of gene expression will be analyzed. We propose that transcription and the correct processing as well as packaging of the newly synthesized mRNA into an mRNP control the translation of this mRNA in the cytoplasm thus coupling intranuclear events in mRNA biogenesis to translation. Recently, we showed that the transcription elongation factor Ctk1 functions as a positive factor in translation elongation by phosphorylating the ribosomal protein Rps2. According to our model, Ctk1 enhances the translation fidelity of mRNAs that have been correctly processed and assembled into mRNPs in the nucleus. In the project proposed here we will analyze how the function of Ctk1 couples transcription to translation and how Ctk1 functions in translation initiation, in support of which we have already obtained evidence. Importantly, we will identify additional players in coupling intranuclear mRNA biogenesis events to translation and unravel their molecular function. In addition, we will determine phosphorylated residues on ribosomal proteins and translation factors, identify their kinases and phosphatases, and analyze the biological significance of these phosphorylation events in translation. Moreover, the conservation in higher eukaryotes of the biological principles obtained with our model organism S. cerevisiae will be assessed. All these experiments are performed under the aspect that the cell uses phosphorylation of ribosomal proteins and translation factors to control the efficient and correct translation of a correctly processed mRNP providing a novel level of gene expression control in eukaryotes.