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      The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.

      Cell

      Animals, Base Sequence, Caenorhabditis, embryology, genetics, DNA Primers, chemistry, Gene Expression Regulation, Genes, Helminth, Helminth Proteins, Hydrogen Bonding, Molecular Sequence Data, Nucleic Acid Conformation, Phylogeny, Protein Biosynthesis, RNA, Antisense, RNA, Messenger, Time Factors, Sequence Alignment, Sequence Homology, Nucleic Acid

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          Abstract

          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.

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          8252621

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