Co-translational assembly of mammalian nuclear multisubunit complexes

Nat Commun. 2019 Apr 15;10(1):1740. doi: 10.1038/s41467-019-09749-y.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exodeoxyribonucleases / chemistry
  • Exodeoxyribonucleases / metabolism
  • HeLa Cells
  • Humans
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism
  • Protein Domains
  • Protein Folding
  • Protein Multimerization*
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism*
  • TATA-Binding Protein Associated Factors / chemistry
  • TATA-Binding Protein Associated Factors / metabolism
  • Transcription Factor TFIID / chemistry
  • Transcription Factor TFIID / metabolism


  • Phosphoproteins
  • Protein Subunits
  • TAF10 protein, human
  • TAF8 protein, human
  • TATA-Binding Protein Associated Factors
  • Transcription Factor TFIID
  • Exodeoxyribonucleases
  • TREX2 protein, human