Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA

Two small RNAs regulate the timing of Caenorhabditis elegans development(1, 2). Transition from the first to the second larval stage fates requires the 22-nucleotide lin-4 RNA(1,3,4), and transition from late larval to adult c ell fates requires the 21-nucleotide let-7 RNA 2. The lin-4 and let-7 RNA g enes are not homologous to each other, but are each complementary to sequen ces in the 3' untranslated regions of a set of protein-coding target genes that are normally negatively regulated by the RNAs1,2,5,6. Here we have det ected let-7 RNAs of similar to 21 nucleotides in samples from a wide range of animal species, including vertebrate, ascidian, hemichordate, mollusc, a nnelid and arthropod, but not in RNAs from several cnidarian and poriferan species, Saccharomyces cerevisiae, Escherichia coli or Arabidopsis. We did not detect lin-4 RNA in these species. We found that let-7 temporal regulat ion is also conserved: let-7 RNA expression is first detected at late larva l stages in C. elegans and Drosophila, at 48 hours after fertilization in z ebrafish, and in adult stages of annelids and molluscs. The let-7 regulator y RNA may control late temporal transitions during development across anima l phylogeny.