Cell
Volume 75, Issue 5, 3 December 1993, Pages 843-854
Journal home page for Cell

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

https://doi.org/10.1016/0092-8674(93)90529-YGet rights and content

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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    The first two authors contributed equally to this work.

    Present address: Dartmouth College Department of Biology, Hanover, New Hampshire 03755.

    Present address: Massachusetts General Hospital Department of Molecular Biology, Boston, Massachusetts 02114

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