The chaperonin CCT interacts with and mediates the correct folding and activity of three subunits of translation initiation factor eIF3; 3b, 3i and 3h

Eukaryotic initiation factor 3 (eIF3) is the largest and most complex eukaryotic mRNA translation factor in terms of the number of protein components or subunits. In mammals eIF3 is composed of thirteen different polypeptide subunits five of which, a, b, c, g and i, are conserved and essential in vivo from yeasts to mammals. Here we show that the eukaryotic cytosolic chaperonin CCT binds to newly synthesised eIF3b and promotes the correct folding of eIF3h and eIF3i. Interestingly, over-expression of the latter two subunits is associated with enhanced translation of specific mRNAs over and above the general enhancement of global translation. In agreement with this, our data show that as CCT is required for the correct folding of eIF3h and eIF3i subunits it indirectly influences gene expression with eIF3i overexpression enhancing both cap- and IRES-dependent translation initiation while eIF3h overexpression selectively increases IRES-dependent translation initiation. Importantly, these studies demonstrate the requirement of the chaperonin machinery for the correct folding of essential components of the translational machinery and provide further evidence of the close interplay between the cell environment, cell signalling, cell proliferation, the chaperone machinery and translational apparatus.

Source: BJ Cell - December 10, 2013 Category: Biochemistry Authors: A Roobol, J Roobol, M J Carden, M E Smith, J WB Hershey, A Bastide, J RP Knight, A E Willis, C Mark Smales Tags: BJ Cell Source Type: research