Not miR-ly muscular: microRNAs and muscle development (original) (raw)

  1. Julius Brennecke,
  2. Alexander Stark, and
  3. Stephen M. Cohen1
  4. European Molecular Biology Laboratory, 69117 Heidelberg, Germany

Precision in spatial and temporal control of gene expression is important for formation of tissues and organs. Roughly 5% of the known gene complement in animals encodes transcriptional activators and repressors, whose combinatorial action controls the expression of target genes, triggering cell-fate decisions and differentiation during development. With the discovery of microRNAs, a new means of regulating gene expression has been introduced (for review, see Lai 2003; Ambros 2004; Bartel 2004). These ∼22-nucleotide-long RNAs are now thought to comprise 1%-5% of the known genes in organisms ranging from nematodes and flies to mammals (Bartel 2004; Berezikov et al. 2005; Xie et al. 2005). microRNAs have been shown to act as negative regulators of target gene expression by recruiting silencing complexes to complementary sequence elements in target mRNAs. Bioinformatic studies have demonstrated that the average animal miRNA has hundreds of target genes, so that up to 30% of all animal genes are miRNA targets (Brennecke et al. 2005; Grün et al. 2005; Krek et al. 2005; Lewis et al. 2005; Xie et al. 2005). Considering that target sites often occur in a combinatorial fashion, these findings suggest an enormous regulatory potential for miRNAs in gene expression programs, rivaling the complexity of the transcriptional control network. But what do they do?

miRNAs are expressed in essentially every cell type analyzed to date. A recent systematic analysis of spatial expression of miRNAs in zebrafish larvae showed that most, if not all, tissues and organs express a unique miRNA complement (Wienholds et al. 2005). Not surprisingly, individual miRNAs have been implicated in a variety of developmental and physiological processes, including control of developmental timing, cell proliferation, cell fate specification, apoptosis, morphogenesis, fat metabolism, insulin secretion, and cancer (Lee et al. 1993; Wightman et al. 1993 …