C. elegansLIN-66 mediates EIF-3.G-dependent protein translation via a cold-shock domain

Abstract

SummaryProtein translation initiation is a complex and conserved process involving many proteins acting in concert. The eukaryotic initiation factor 3 (eIF3) complex is essential for the assembly of the pre-initiation complex that scans and positions mRNA at the initiation codon. eIF3 complex consists of 13 subunits. In addition to their essential roles in general translation initiation, emerging studies suggest that individual subunits of eIF3 can provide specialized functions in response to specific stimuli. We have previously reported that a gain-of-function (gf) mutation in the G subunit ofC. eleganseIF3 complex,eif-3.g(gf),selectively modulates protein translation in the ventral cord cholinergic motor neurons. Here, through unbiased genetic suppressor screening, we have identified thelin-66gene that mediates theeif-3.g(gf)-dependent protein translation in the motor neurons. LIN-66 is previously reported to be a nematode-specific protein composed of largely low complexity amino acid sequences with unknown functional domains. We combined bioinformatic analysis within vivofunctional dissection and identified a cold-shock domain in LIN-66 to be critical for its function. In the cholinergic motor neurons, LIN-66 shows somatic cytoplasmic localization and close association with EIF-3.G. The low complexity amino acid sequences of LIN-66 modulate its subcellular pattern. Cold-shock-domains are known to interact with RNA and have broad functions in RNA metabolism and protein translation. We propose that LIN-66 mediates stimuli-dependent protein translation by facilitating the interaction of mRNAs with EIF-3.G.