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

  title={Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA},
  author={Amy E Pasquinelli and Brenda J. Reinhart and Frank J. Slack and Mark Q. Martindale and Mitzi I. Kuroda and Betsy Maller and David C. Hayward and Eldon E. Ball and Bernard M. Degnan and Peter M{\"u}ller and J{\"u}rg Spring and Ashok Srinivasan and Mark C. Fishman and John R. Finnerty and Joseph C. Corbo and Michael S. Levine and Patrick S. Leahy and Eric H. Davidson and Gary Ruvkun},
Two small RNAs regulate the timing of Caenorhabditis elegans development. Transition from the first to the second larval stage fates requires the 22-nucleotide lin-4 RNA, and transition from late larval to adult cell fates requires the 21-nucleotide let-7 RNA. 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 RNAs. Here we… 

The expression of the let-7 small regulatory RNA is controlled by ecdysone during metamorphosis in Drosophila melanogaster.

An interaction between steroid hormone signaling and the heterochronic pathway in insects is demonstrated, indicating that the ecdysone pathway regulates the temporal expression of let-7 in Drosophila.

Great expectations of small RNAs

  • A. Schuldt
  • Biology
    Nature Reviews Molecular Cell Biology
  • 2010
The idea that miRNAs have many targets and act to destabilize mRNA, was heretic at the time but turned out to be exactly right, suggests that the authors may be right to have such high hopes for these small RNAs.

C. elegans microRNAs.

MicroRNAs (miRNAs) are small, non-coding regulatory RNAs found in many phyla that control such diverse events as development, metabolism, cell fate and cell death. They have also been implicated in



The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation.

The results indicate that association of lin-4 RNA with the 3' UTR of Lin-14 mRNA permits normal biogenesis of lin -14 mRNA, and normal translational initiation, but inhibits step(s) thereafter, such as translational elongation and/or the release of stable LIN-14 protein.

An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells

It is shown that ‘loss-of-function’ phenotypes can be created in cultured Drosophila cells by transfection with specific double-stranded RNAs, which coincides with a marked reduction in the level of cognate cellular messenger RNAs.

Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans

To their surprise, it was found that double-stranded RNA was substantially more effective at producing interference than was either strand individually, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process.

Targeted mRNA degradation by double-stranded RNA in vitro.

The development of a cell-free system from syncytial blastoderm Drosophila embryos that recapitulates many of the features of RNAi is reported, demonstrating that RNAi can be mediated by sequence-specific processes in soluble reactions.

The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events.

The results of gene dosage, complementation, and temperature-shift experiments indicate that the fates expressed by cells at successive stages of these cell lineages are specified by the level of lin- 14 activity and that lin-14 acts at multiple times during development to control stage-specific choices of cell fate.