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Published online before print April 22, 2004, 10.1101/gad.1188404
GENES & DEVELOPMENT 18:1047-1059, 2004
©2004 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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RESEARCH PAPER

Translation repression by GLD-1 protects its mRNA targets from nonsense-mediated mRNA decay in C. elegans

Min-Ho Lee and Tim Schedl1

Department of Genetics, Washington University School of Medicine, Saint Louis, Missouri 63110, USA

Previously, we identified multiple in vivo mRNA targets of the maxi-KH/STAR domain protein GLD-1 by their ability to interact with GLD-1 in cytoplasmic extracts and, for all targets tested thus far, GLD-1 functions as a translational repressor. However, here we show that GLD-1 stabilizes the mRNAs of two targets, gna-2 (T23G11.2) and Y75B12B.1. gna-2 mRNA has two upstream open reading frames (uORF), resulting in two premature stop codons. We found that gna-2 mRNA is a naturally occurring mRNA target of nonsense-mediated mRNA decay (NMD) and that the binding of GLD-1 protects gna-2 mRNA from NMD, likely by repressing translation of the uORFs. Therefore, gna-2 mRNA comes under two posttranscriptional controls: (1) translation regulation by a specific translational repressor, GLD-1; and (2) uORF elicited regulation, mainly through NMD. As a result, these two posttranscriptional controls together provide precise temporal and spatial control of gene expression. Consistent with this novel mode of regulation, when GLD-1 mRNA targets acquire premature stop codon mutations, GLD-1 protects them from NMD. Analysis of several mRNA targets containing premature stop codons suggests that in translation repression, GLD-1 either represses ribosome assembly on the target mRNA, or subsequent ribosome elongation to the premature stop codon.

[Keywords: Germ line; translation repression; upstream open reading frame; nonsense-mediated mRNA decay; gld-1; gna-2]

Received January 22, 2004; revised version accepted March 23, 2004.


Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1188404.

Supplemental material is available at http://www.genesdev.org.

1 Corresponding author.
E-MAIL ts{at}genetics.wustl.edu; FAX (314) 362-7875.


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