The STAR protein QKI-6 is a translational repressor

Abstract

The signal transduction and activation of RNA (STAR) family of RNA-binding proteins, whose members are evolutionarily conserved from yeast to humans, are important for a number of developmental decisions. For example, in the mouse, quaking proteins (QKI-5, QKI-6, and QKI-7) are essential for embryogenesis and myelination , whereas a closely related protein in Caenorhabditis elegans, germline defective-1 (GLD-1), is necessary for germline development. Recently, GLD-1 was found to be a translational repressor that acts through regulatory elements, called TGEs (for tra-2 and GLI elements), present in the 3 untranslated region of the sex-determining gene tra-2. This gene promotes female development, and repression of tra-2 translation by TGEs is necessary for the male cell fates. The finding that GLD-1 inhibits tra-2 translation raises the possibility that other STAR family members act by a similar mechanism to control gene activity. Here we demonstrate, both in vitro and in vivo, that QKI-6 functions in the same manner as GLD-1 and can specifically bind to TGEs to repress translation of reporter constructs containing TGEs. In addition, expression of QKI-6 in C. elegans wild-type hermaphrodites or in hermaphrodites that are partially masculinized by a loss-of-function mutation in the sex-determining gene tra-3 results in masculinization of somatic tissues, consistent with QKI-6 repressing the activity of tra-2. These results strongly suggest that QKI-6 may control gene activity by operating through TGEs to regulate translation. In addition, our data support the hypothesis that other STAR family members may also be TGE-dependent translational regulators.quaking ͉ myelination ͉ mouse ͉ translation control ͉ tra-2 and GLI element (TGE)

The Quaking I-5 Protein (QKI-5) Has a Novel Nuclear Localization Signal and Shuttles between the Nucleus and the Cytoplasm

“…The QKI-5 kt4 mutation loses the ability to self-interact; however, it retains the ability to bind RNA (45). When GFP was fused with QKI-5 kt4 and transfected into HeLa cells, the localization of GFP-QKI-5 kt4 is the same as wild type QKI-5 (Fig.…”

“…Another family member from C. elegans, GLD-1, which is solely cytoplasmic, has recently been shown to repress translation of specific mRNAs by binding to the tra-2 and GLI elements (TGE) in their 3Ј-untranslated region (44). Likewise, QKI-6 has been found to have the same function in transgenic C. elegans (45). Finally, SAM68 has been recently shown to substitute for HIV-1 Rev protein in facilitating the nuclear export of HIV-1 RNA (46).…”

Specificity of the STAR/GSG domain protein Qk1: Implications for the regulation of myelination

“…In a published report, Qk1-6 (6-kb isoform) was shown to functionally substitute for GLD-1 in the repression of a reporter gene containing the tra-2 3Ј-UTR in transgenic worms (Saccomanno et al 1999). Given this result and the strong similarity between GLD-1 and Qk1, it seemed likely that Qk1 might also bind the TGE with high affinity.…”

Developmental genetics of the mouse <i>t</i>-complex

“…The qk mutation is due to a 1-Mb deletion in the regulatory element of a gene encoding the RNA-binding protein QKI (Ebersole et al, 1996). QKI is believed to regulate pre-mRNA splicing (Wu et al, 2002), mRNA stability (Li et al, 2000;Larocque et al, 2005), nuclear mRNA export (Larocque et al, 2002) and translation repression (Saccomanno et al, 1999). Homozygotes of N-ethyl-N-nitrosourea (ENU)-mutagenized or targeted deficient alleles exhibit a deficiency of vasculogenesis in the yolk sac and die at around embryonic day (E)10.5 (Noveroske et al, 2002;Li et al, 2003).…”