Seminar by Prof. Martine Collart "Co-translational assembly of the proteasome needs the Not4 subunit of the Ccr4-Not complex and is essential for solubility of new proteins"

Title: "Co-translational assembly of the proteasome needs the Not4 subunit of the Ccr4-Not complex and is essential for solubility of new proteins"

Speaker:Prof. Martine Collart

Affiliation:University of Geneva Medical School

Abstract:

Ribosome movement along mRNAs occurs with pauses for vectorial folding of nascent chains. Occasionally stalling causes translation termination and degradation of peptide and mRNA. Not4 is a an E3 ligase connected with co-translational quality control. It is a subunit of the Ccr4-Not complex, a stable component of the complex in budding yeast but not in metazoans and flies. However the metazoan Not4 complements the yeast null mutant indicating that Not4 function is conserved. We used RNA PAR-CLIP, ribosome profiling, and SILAC to determine the role of Not4 during translation. We show that Not4 functions through mRNA binding and associates with mRNAs during transcription and translation. In the absence of Not4 we observe that highly produced proteins are produced with less ribosome pausing and tend to aggregate. Analyzing proteasome subunit-encoding mRNAs as an example, we show that ribosomes pause for exposed nascent domains to interact co-translationally. Not4 regulates ribosome movement preceding these ribosome-pause sites, to ensure appropriate folding for assembly of the proteins into complexes. This is in particular true for the proteasome. These results define Not4 as a critical regulator of translation elongation and soluble protein production 

Biography: 

Master of Biochemistry at Geneva University, Faculty of Science, 1985

PhD in Molecular Biology at Geneva University, Faculty of Medicine, 1990  (“Regulation of gene expression in mouse macrophages”)

Post-doctoral fellow at Harvard Medical School, 1990-1993

Independent group leader at Geneva University, Faculty of Medicine, 1993

Associate professor, at Geneva University, Faculty of Medicine, 2004

Full professor, at Geneva University, Faculty of Medicine 2011