Co-translation drives the assembly of mammalian nuclear multisubunit complexes

Abstract

Cells dedicate significant energy to build proteins often organized in multiprotein assemblies with tightly regulated stoichiometries. As genes encoding proteins assembling in the same multisubunit complexes are dispersed in the genome of eukaryotes, it is unclear how multisubunit complexes assemble. 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 cotranslationally. We demonstrate that the dimerization domains and their positions in the interacting subunits determine the co-translational assembly pathway (simultaneous or sequential). Our results indicate that protein translation and complex assembly are linked in building mammalian multisubunit complexes and suggest that co-translational assembly is a general principle in mammalian cells to avoid non-specific interactions and protein aggregation. These findings will significantly advance structural biology by defining endogenous co-translational building blocks in the architecture of multisubunit complexes.

Interactions between nascent proteins translated by adjacent ribosomes drive homomer assembly

“…The absence of a known partner subunit may be caused by the less complete structural characterization of heteromeric complexes. We also did not find clear evidence that the recently described assembly of TAF6-TAF9 nuclear complex includes nascent chain interactions (14). Both subunits are included in the low confidence list, but the length of the disome shift and the enrichment efficiency is very different between the two proteins, which does not agree with a model of co-co assembly in trans.…”

“…3D, right). While these findings do not exclude the possibility that individual heteromers co-co assemble, as previously reported (13,14,19), they rather suggest that co-co assembly is predominantly employed for the formation of homomeric protein complexes.…”

Translating Messages in Different Neighborhoods

“…Altogether, these findings reiterate the close links between mRNA targeting and translational dynamics, while also revealing that sites of localized translation may represent hubs for the assembly and interplay of functional protein modules. These findings are consistent with recent studies documenting several examples of co-translational protein complex assembly (Kamenova et al, 2019;Shiber et al, 2018). Elucidating the mechanisms coordinating the spatio-temporal dynamics of mRNA trafficking and translation with protein module assembly will be an exciting line of future investigation with potentially broad impacts on our understanding of cellular organization.…”

Spatial organization of the transcriptome in individual neurons

“…It is made The copyright holder for this preprint this version posted December 7, 2020. ; https://doi.org/10.1101/2020.12.07.414060 doi: bioRxiv preprint 10 interactions between nascent peptides while these proteins were synthesized. For protein complexes made of distinct subunits, the interaction of nascent polypeptides during protein synthesis could bring the encoding mRNAs into proximity (32,33). This mechanism could thus contribute to the formation of clusters I and II given our observation of their dependence on protein synthesis.…”