Biosynthesis of the translation machinery: identification of regulatory factors and mechanisms

• Applicant: Professor Dr. Utz Fischer
• Subject Area: Cell Biology
• Term: from 2007 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 33442413

The synthesis of many mammalian proteins associated with the translational apparatus (ribosomal proteins and elongation factors) is selectively regulated at the translational level by mitogenic and nutritional signals. The corresponding mRNAs are characterized by the presence of a unique se-quence element, termed the 5' Terminal OligoPyrimidine tract (5'TOP), which comprises the core of the translational cis-regulatory element. The translational control of TOP mRNAs is manifested by their selective and reversible shift from polysomes in dividing cells into subpolysomal mRNP particles in quiescent cells or upon starvation. However, neither the mechanisms that regulate TOP mRNA trans-lation nor transacting factors involved have been identified. We have established strategies to purify TOP motif-binding factors and to test their activity in translation of TOP mRNAs. Data obtained in the previous funding period suggest that TOP mRNA translation requires positively acting factors, which bind in a phosphorylation-dependent manner to the TOP motif. The identification of this factor and its mode of action in TOP mRNA regulation is the major task of this project.

• DFG Programme: Research Units
• Subproject of: FOR 855: Cytoplasmic Regulation of Gene Expression