The manufacture of multi-protein complexes: a new assembly method unveiled
April 15, 2019
The assembly of proteins into large macromolecular complexes is essential to the viability of cells. However, since genes encoding proteins that constitute such multiprotein complexes are dispersed in the eukaryotic genome, it is difficult to understand how these subunits can assemble. In this study, Laszlo Tora's team at the IGBMC (CNRS/Inserm/Université de Strasbourg) determined a pathway for assembling mammalian transcription complexes (TFIID, SAGA and TREX-2), each composed of a large number of subunits. According to their observations, complex assembly would be carried out during the synthesis of the proteins that constitute these complexes. These results are published in Nature Communications on April 15, 2019.
Protein synthesis is carried out in several stages. The genes encoding each protein are first transcribed in the nucleus. The messenger RNAs resulting from this transcription are exported to the cytoplasm, where they are translated into proteins by ribosomes. Once synthesized, most proteins don’t act alone in the cell, they generally function as components of large complexes whose formation must be cleverly orchestrated. To better understand cellular functions, it is essential to study the precise mechanism that guides the formation of these multiprotein assemblies. Indeed, protein folding and complex formation must be a precisely regulated process in the cell to avoid non-specific interactions and also because a single protein can interact in some cases with different partners.
In this study, Laszlo Tora’s team studied the assembly of three multi-protein complexes associated with RNA polymerase II transcription in mammals: TFIID, TREX-2 and SAGA. They demonstrated that these complexes were assembled while the messenger RNAs coding for interacting proteins are translated by ribosomes, according to two models, simultaneous or sequential. In the first case, the two subunits assemble simultaneously during their translation, suggesting that the ribosomes that synthesize them are in close physical proximity. In the second case, a protein already synthesized interacts with a protein being translated.
These results indicate that certain subunits of complexes associated with mammalian transcription, such as TFIID, SAGA and TREX-2, are assembled during translation. This co-translational assembly of protein complexes seems to be a mechanism common to all eukaryotic cells, which would not only control protein interactions, but also avoid their aggregation and ensure their correct proportion in the cell.
This study was funded by the ANR, ERC, ARC Cancer Research Foundation.