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

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Two small RNAs regulate the timing of Caenorhabditis elegans development1,2. Transition from the first to the second larval stage fates requires the 22-nucleotide lin-4 RNA1,3,4, and transition from late larval to adult cell fates requires the 21-nucleotide let-7 RNA2. The lin-4 and let-7 RNA genes are not homologous to each other, but are each complementary to sequences 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 detected let-7 RNAs of 21 nucleotides in samples from a wide range of animal species, including vertebrate, ascidian, hemichordate, mollusc, annelid 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 regulation is also conserved: let-7 RNA expression is first detected at late larval stages in C. elegans and Drosophila , at 48 hours after fertilization in zebrafish, and in adult stages of annelids and molluscs. The let-7 regulatory RNA may control late temporal transitions during development across animal phylogeny.

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Figure 1: let-7 gene sequences.
Figure 2: Expression of let-7 RNA in human and Drosophila.
Figure 3: Expression of let-7 RNA is developmentally regulated in lophotrochozoans and deuterostomes.
Figure 4: Phylogenetic comparison of let-7 RNA expression.


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We thank the following people for RNA and tissue samples: T. Heanue, R. Pearse and C. Tabin for chick; J. Gerhart and M. Kirschner for Xenopus and acorn worm; S. Agarwal for Xenopus; N. Stavropoulos for mouse; C. Unabia and K. del Carmen for annelid and mollusc; H. Bode for Hydra; J. Nardone and S. Ferrari for Arabidopsis; P. Sudarsanam for yeast; and D. Selinger for E. coli. The phylogenetic survey in this work was inspired by the NASA Evolution and Development meetings organized by E. Davidson and C. Golden. This work was supported by an NIH grant from NIGMS to G.R. and a grant from the MGH Fund for Medical Discovery to A.E.P.

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Correspondence to Gary Ruvkun.

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