Translation repression by GLD-1 protects its mRNA targets from nonsense-mediated mRNA decay in C. elegans.
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.
Lee
Min-Ho
MH
Department of Genetics, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
Schedl
Tim
T
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D018389:Codon, Nonsense; D018509:DNA, Helminth / Q000235:genetics; D017238:Genes, Helminth; D008954:Models, Biological; D016366:Open Reading Frames; D014176:Protein Biosynthesis; D020871:RNA Stability; D018510:RNA, Helminth / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; D018389:Codon, Nonsense; D018509:DNA, Helminth; C094448:GLD-1 protein, C elegans; D018510:RNA, Helminth; D012333:RNA, Messenger; D012097:Repressor Proteins