Abstract
The binding of the STAR protein GLD-1 to an element in the tra-2 3′ untranslated region (3′UTR), called the TGE ( tra GLI element), represses tra-2 translation, allowing for hermaphrodite spermatogenesis in Caenorhabditis elegans. GLD-1 is a member of the STAR family that includes the mammalian quaking (Qk) proteins. Here, we show that the 3′UTR of the nematode homologue of GLI1, called tra-1, also contains a TGE, through which translation is regulated by GLD-1. We find that GLD-1 activity is required for proper TRA-1 protein expression in hermaphrodites. RNA gel shift assays show that GLD-1 binds the predicted sites. Using reporter transgenes, we show that the human GLI1 ( hGLI1) 3′UTR controls translation in the mouse embryo. We demonstrate that the addition of the mouse QK isoform-6 (QKI-6) protein to a mammalian cell line that lacks QKI-6 can confer regulation on reporter and GLI1 mRNAs in a TGE-specific manner, and reduction of QKI-6 activity with siRNA disrupts translational control. Further, siRNA knockdown of QKI-6 increases the activity of a reporter transgene that monitors the transcriptional activity of mouse Gli1 ( mGli1) and increases mouse Gli1 protein. We show by immunoprecipitation that QKI-6 antibody specifically co-purifies TGE-containing mRNAs in ribonucleoproteins. Thus, we find that the mouse QKI-6 protein acts through the mGli1 and hGLI1 RNAs to repress translation. Our results suggest that STAR family-dependent translational control of GLI mRNAs is ancient, and that it existed before the division of nematodes and mammals.
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