Final Report Summary - REGEXTRA (A Novel Level for the Regulation of Eukaryotic Gene Expression: Coupling Transcription to Translation) Gene expression is the process by which the genetic information stored in our genes is given a “voice” and is thus a fundamental process of life. During this process the genetic information stored in the DNA is first transcribed into messenger RNA (mRNA) – one kind of mRNA for each gene. These “messengers” are then decoded by cellular “machines” called ribosomes. The ribosomes use the information stored in the mRNA to synthesize a corresponding polypeptide chain by linking different amino acids to each other. These polypeptide chains – or proteins – are the work horses of the cell, fulfilling the different tasks needed for cellular survival and propagation.Consequently, transcription of DNA into mRNA and translation of mRNA into protein by the ribosomes have to be efficient and very accurate. In this project, we studied:1. A possible connection between transcription and translation that renders gene expression more efficient and accurate, and2. phosphorylation, a protein modification, of ribosomes as a novel mechanism to regulate translation.Previously, we showed that Ctk1, a protein crucial for transcription, has a second function in translation. In the first project we identified Sro9, which has a function transcription and translation, as an interaction partner of Ctk1. We showed that Sro9 is present at the site of transcription and leaves the nucleus together with the mRNA. Thus, Sro9 might also link transcription to translation.In the second project we identified over 300 phosphorylated sites in ribosomal proteins, the building blocks of ribosomes. Phosphorylation is a modification of a certain amino acid of a protein that often regulates its function. We could already show for ten phosphorylated sites that they are important for translation. For two of these, we showed how they function in translation. This is the first time that phosphorylation events in ribosomal proteins have been shown to be important for translation.This work uncovered a novel link between transcription and translation and identified a new way to regulate translation – by phosphorylation of ribosomal proteins. Thus, our results enhance our understanding of gene expression; a process that happens daily in our cells and is essential for all life.
