Human Ccr4-Not complexes contain variable deadenylase subunits

Nga-Chi Lau , Annemieke Kolkman , Frederick M.A. van Schaik , Klaas W. Mulder , W.W.M. Pim Pijnappel , Albert J.R. Heck , H.Th. Marc Timmers (1)

1 Department of Physiological Chemistry

The Ccr4-Not complex is evolutionary conserved and important for regulation of mRNA synthesis and decay. The composition of the yeast complex has been well described. Orthologs of the yeast Ccr4-Not components have been identified in human cells including multiple subunits with mRNA deadenylase activity. In this study, we examine the composition of the human Ccr4-Not complex in an in-depth proteomic approach using stable cell lines expressing tagged CNOT proteins. We find at least four different variants of the human complex, consisting of seven stable core proteins and mutually-exclusive associated mRNA deadenylase subunits. Interestingly, human CNOT4 is in a separate ~200 kDa complex. Furthermore, analyses of associated proteins indicate involvement of Ccr4-Not complexes in splicing, transport and localization of RNA molecules. Taken together, human Ccr4-Not complexes are heterogeneous in composition due to differences in their deadenylase subunits, which may reflect the multi-functionality of these complexes in cellular processes.

Mots clés: Life Sciences

Nga-Chi Lau, Annemieke Kolkman, Frederick M.A. van Schaik, Klaas W. Mulder, W.W.M. Pim Pijnappel, et al.. Human Ccr4-Not complexes contain variable deadenylase subunits. Biochemical Journal, 2009, 422 (3), pp.443-453. ⟨10.1042/BJ20090500⟩. ⟨hal-00479183⟩