The STAR protein QKI-6 is a translational repressor

The STAR protein QKI-6 is a translational repressor

^*Department of Cell and Molecular Biology and the Lurie Cancer Center, Northwestern University Medical School, Chicago, IL 60611; and ^†Institute of Cellular and Molecular Biology, Department of Microbiology, University of Texas, Austin, TX 78712

Edited by Judith Kimble, University of Wisconsin, Madison, WI, and approved August 16, 1999 (received for review January 20, 1999)

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 germ-line 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.

Footnotes

↵ ‡ To whom reprint requests should be addressed. E-mail: ebg778{at}nwu.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

TGE,

tra-2 and GLI element;

β-gal,

β-galactosidase;

3′UTR,

3′ untranslated region;

STAR,

signal transduction and activation of RNA;

GLD-1,

germline defective-1;

tra-2,

transformer