The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.
lin-4 is essential for the normal temporal control of diverse postembryonic developmental events in C. elegans. lin-4 acts by negatively regulating the level of LIN-14 protein, creating a temporal decrease in LIN-14 protein starting in the first larval stage (L1). We have cloned the C. elegans lin-4 locus by chromosomal walking and transformation rescue. We used the C. elegans clone to isolate the gene from three other Caenorhabditis species; all four Caenorhabditis clones functionally rescue the lin-4 null allele of C. elegans. Comparison of the lin-4 genomic sequence from these four species and site-directed mutagenesis of potential open reading frames indicated that lin-4 does not encode a protein. Two small lin-4 transcripts of approximately 22 and 61 nt were identified in C. elegans and found to contain sequences complementary to a repeated sequence element in the 3' untranslated region (UTR) of lin-14 mRNA, suggesting that lin-4 regulates lin-14 translation via an antisense RNA-RNA interaction.
Lee
R C
RC
Harvard University, Department of Cellular and Developmental Biology, Cambridge, Massachusetts 02138.
Feinbaum
R L
RL
Ambros
V
V
D000818:Animals; D001483:Base Sequence; D002107:Caenorhabditis / Q000196:embryology / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000235:genetics*; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D014176:Protein Biosynthesis; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013997:Time Factors
D017931:DNA Primers; D015801:Helminth Proteins; D016372:RNA, Antisense; D012333:RNA, Messenger