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Gene Review

let-7  -  ncRNA

Drosophila melanogaster

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Disease relevance of let-7

  • Here we have detected let-7 RNAs of approximately 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 [1].
 

High impact information on let-7

  • In C. elegans, a homolog of the well-known fly developmental regulator hunchback acts downstream of the microRNAs lin-4 and let-7 in a pathway controlling developmental timing [2].
  • The let-7 regulatory RNA may control late temporal transitions during development across animal phylogeny [1].
  • Targeted destruction in cultured human cells of the messenger RNA encoding the enzyme Dicer, which acts in the RNA interference pathway, leads to accumulation of the let-7 precursor [3].
  • The miRNAs have diverse expression patterns during development: a let-7 paralog is temporally coexpressed with let-7; miRNAs encoded in a single genomic cluster are coexpressed during embryogenesis; and still other miRNAs are expressed constitutively throughout development [4].
  • In S2 cells, Ecd and the juvenile hormone analog methoprene exert opposite effects on the expression of these four miRNAs, indicating the participation of both these hormones in the temporal regulation of mir-34, -100, -125, and let-7 expression in vivo [5].
 

Biological context of let-7

 

Anatomical context of let-7

 

Associations of let-7 with chemical compounds

  • Here, we ask whether the steroid hormone ecdysone induces let-7 or miR-125 expression at the onset of metamorphosis, attempting to link a known temporal regulator in Drosophila with the heterochronic pathway defined in C. elegans [8].
  • We identify the abrupt (ab) gene, encoding a nuclear protein, as a bona fide let-7 target and provide evidence that let-7 governs the maturation rate of abdominal NMJs during metamorphosis by regulating ab expression [9].
 

Other interactions of let-7

  • We show that ecdysone and BR-C are required for let-7 expression, indicating that the ecdysone pathway regulates the temporal expression of let-7 in Drosophila [7].
  • We find that let-7 and miR-125 are coordinately expressed in late larvae and prepupae, in synchrony with the high titer ecdysone pulses that initiate metamorphosis [8].

References

  1. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Pasquinelli, A.E., Reinhart, B.J., Slack, F., Martindale, M.Q., Kuroda, M.I., Maller, B., Hayward, D.C., Ball, E.E., Degnan, B., Müller, P., Spring, J., Srinivasan, A., Fishman, M., Finnerty, J., Corbo, J., Levine, M., Leahy, P., Davidson, E., Ruvkun, G. Nature (2000) [Pubmed]
  2. MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Ambros, V. Cell (2003) [Pubmed]
  3. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Hutvágner, G., McLachlan, J., Pasquinelli, A.E., Bálint, E., Tuschl, T., Zamore, P.D. Science (2001) [Pubmed]
  4. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Lau, N.C., Lim, L.P., Weinstein, E.G., Bartel, D.P. Science (2001) [Pubmed]
  5. Temporal regulation of microRNA expression in Drosophila melanogaster mediated by hormonal signals and broad-Complex gene activity. Sempere, L.F., Sokol, N.S., Dubrovsky, E.B., Berger, E.M., Ambros, V. Dev. Biol. (2003) [Pubmed]
  6. The C elegans hunchback homolog, hbl-1, controls temporal patterning and is a probable microRNA target. Lin, S.Y., Johnson, S.M., Abraham, M., Vella, M.C., Pasquinelli, A., Gamberi, C., Gottlieb, E., Slack, F.J. Dev. Cell (2003) [Pubmed]
  7. The expression of the let-7 small regulatory RNA is controlled by ecdysone during metamorphosis in Drosophila melanogaster. Sempere, L.F., Dubrovsky, E.B., Dubrovskaya, V.A., Berger, E.M., Ambros, V. Dev. Biol. (2002) [Pubmed]
  8. Coordinate regulation of small temporal RNAs at the onset of Drosophila metamorphosis. Bashirullah, A., Pasquinelli, A.E., Kiger, A.A., Perrimon, N., Ruvkun, G., Thummel, C.S. Dev. Biol. (2003) [Pubmed]
  9. Temporal regulation of metamorphic processes in Drosophila by the let-7 and miR-125 heterochronic microRNAs. Caygill, E.E., Johnston, L.A. Curr. Biol. (2008) [Pubmed]
 
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