C. elegans LIN-66 mediates EIF-3/eIF3-dependent protein translation via a cold-shock domain

• Published in: Life science alliance 2024-09, Vol.7 (9), p.e202402673
• Main Authors: Blazie, Stephen M, Fortunati, Daniel, Zhao, Yan, Jin, Yishi
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cold-Shock Response; Eukaryotic Initiation Factor-3 - genetics; Eukaryotic Initiation Factor-3 - metabolism; Motor Neurons - metabolism; Mutation; Protein Biosynthesis; Protein Domains; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 2575-1077; 2575-1077
• DOI: 10.26508/lsa.202402673

Protein translation initiation is a conserved process involving many proteins acting in concert. The 13 subunit eukaryotic initiation factor 3 (eIF3) complex is essential for assembly of the pre-initiation complex that scans mRNA and positions ribosome at the initiation codon. We previously reported that a gain-of-function (gf) mutation affecting the G subunit of the eIF3 complex, , selectively modulates protein translation in the ventral cord cholinergic motor neurons. Here, through unbiased genetic suppressor screening, we identified that the gene mediates ( )-dependent protein translation in motor neurons. LIN-66 is composed largely of low-complexity amino acid sequences with unknown functional domains. We combined bioinformatics analysis with in vivo functional dissection and identified a cold-shock domain in LIN-66 critical for its function. In cholinergic motor neurons, LIN-66 shows a close association with EIF-3.G in the cytoplasm. The low-complexity amino acid sequences of LIN-66 modulate its subcellular pattern. As cold-shock domains function broadly in RNA regulation, we propose that LIN-66 mediates stimulus-dependent protein translation by facilitating the interaction of mRNAs with EIF-3.G.