Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans.
During C. elegans development, the temporal pattern of many cell lineages is specified by graded activity of the heterochronic gene Lin-14. Here we demonstrate that a temporal gradient in Lin-14 protein is generated posttranscriptionally by multiple elements in the lin-14 3'UTR that are regulated by the heterochronic gene Lin-4. The lin-14 3'UTR is both necessary and sufficient to confer lin-4-mediated posttranscriptional temporal regulation. The function of the lin-14 3'UTR is conserved between C. elegans and C. briggsae. Among the conserved sequences are seven elements that are each complementary to the lin-4 RNAs. A reporter gene bearing three of these elements shows partial temporal gradient activity. These data suggest a molecular mechanism for Lin-14p temporal gradient formation: the lin-4 RNAs base pair to sites in the lin-14 3'UTR to form multiple RNA duplexes that down-regulate lin-14 translation.
Wightman
B
B
Department of Molecular Biology, Massachusetts General Hospital, Boston 02114.
Ha
I
I
Ruvkun
G
G
D000818:Animals; D001483:Base Sequence; D002107:Caenorhabditis / Q000196:embryology / Q000235:genetics*; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009024:Morphogenesis; D014176:Protein Biosynthesis; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013997:Time Factors
D015801:Helminth Proteins; D016372:RNA, Antisense; D012333:RNA, Messenger