Dampening of expression oscillations by synchronous regulation of a microRNA and its target

Nat Genet. 2013 Nov;45(11):1337-44. doi: 10.1038/ng.2763. Epub 2013 Sep 15.

Abstract

The complexity of multicellular organisms requires precise spatiotemporal regulation of gene expression during development. We find that in the nematode Caenorhabditis elegans approximately 2,000 transcripts undergo expression oscillations synchronized with larval transitions while thousands of genes are expressed in temporal gradients, similar to known timing regulators. By counting transcripts in individual worms, we show that pulsatile expression of the microRNA (miRNA) lin-4 maintains the temporal gradient of its target lin-14 by dampening its expression oscillations. Our results demonstrate that this insulation is optimal when pulsatile expression of the miRNA and its target is synchronous. We propose that such a miRNA-mediated incoherent feed-forward loop is a potent filter that prevents the propagation of potentially deleterious fluctuations in gene expression during the development of an organism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / genetics*
  • Gene Expression Regulation, Developmental
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Nuclear Proteins / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • LIN-14 protein, C elegans
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Messenger
  • lin-4 microRNA, C elegans

Associated data

  • GEO/GSE49043