The timing of lin-4 RNA accumulation controls the timing of postembryonic developmental events in Caenorhabditis elegans.
The lin-4 gene encodes a small RNA that is required to translationally repress lin-14 toward the end of the first larval stage of Caenorhabditis elegans development. To determine if the timing of LIN-14 protein down-regulation depends on the temporal profile of lin-4 RNA level, we analyzed the stage-specificity of lin-4 RNA expression during wild-type development and examined the phenotypes of transgenic worms that overexpress lin-4 RNA during the first larval stage. We found that lin-4 RNA first becomes detectable at approximately 12 h of wild-type larval development and rapidly accumulates to nearly maximum levels by 16 h. This profile of lin-4 RNA accumulation corresponded to the timing of LIN-14 protein down-regulation. Transgenic strains that express elevated levels of lin-4 RNA prior to 12 h of development display reduced levels of LIN-14 protein and precocious phenotypes consistent with abnormally early loss of lin-14 activity. These results indicate that the temporal profile of lin-4 RNA accumulation specifies the timing of LIN-14 down-regulation and thereby controls the timing of postembryonic developmental events.
Feinbaum
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R
Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.
Ambros
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V
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D009687:Nuclear Proteins; D010641:Phenotype; D014176:Protein Biosynthesis; D018510:RNA, Helminth / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; C102669:LIN-14 protein, C elegans; D009687:Nuclear Proteins; D018510:RNA, Helminth; D012333:RNA, Messenger