Co-translational assembly of mammalian nuclear multisubunit complexes

Ivanka Kamenova, Pooja Mukherjee, Sascha Conic, Florian Mueller, Farrah El-Saafin, Paul Bardot, Jean-Marie Garnier, Doulaye Dembele, Simona Capponi, H. T. Marc Timmers, Stéphane D. Vincent and László Tora ()
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Ivanka Kamenova: Institut de Génétique et de Biologie Moléculaire et Cellulaire
Pooja Mukherjee: Institut de Génétique et de Biologie Moléculaire et Cellulaire
Sascha Conic: Institut de Génétique et de Biologie Moléculaire et Cellulaire
Florian Mueller: Département Biologie Cellulaire et Infections
Farrah El-Saafin: Institut de Génétique et de Biologie Moléculaire et Cellulaire
Paul Bardot: Institut de Génétique et de Biologie Moléculaire et Cellulaire
Jean-Marie Garnier: Institut de Génétique et de Biologie Moléculaire et Cellulaire
Doulaye Dembele: Institut de Génétique et de Biologie Moléculaire et Cellulaire
Simona Capponi: Medical Center-University of Freiburg
H. T. Marc Timmers: Medical Center-University of Freiburg
Stéphane D. Vincent: Institut de Génétique et de Biologie Moléculaire et Cellulaire
László Tora: Institut de Génétique et de Biologie Moléculaire et Cellulaire

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Cells dedicate significant energy to build proteins often organized in multiprotein assemblies with tightly regulated stoichiometries. As genes encoding subunits assembling in a multisubunit complex are dispersed in the genome of eukaryotes, it is unclear how these protein complexes assemble. Here, we show that mammalian nuclear transcription complexes (TFIID, TREX-2 and SAGA) composed of a large number of subunits, but lacking precise architectural details are built co-translationally. We demonstrate that dimerization domains and their positions in the interacting subunits determine the co-translational assembly pathway (simultaneous or sequential). The lack of co-translational interaction can lead to degradation of the partner protein. Thus, protein synthesis and complex assembly are linked in building mammalian multisubunit complexes, suggesting that co-translational assembly is a general principle in mammalian cells to avoid non-specific interactions and protein aggregation. These findings will also advance structural biology by defining endogenous co-translational building blocks in the architecture of multisubunit complexes.

Date: 2019
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DOI: 10.1038/s41467-019-09749-y

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