Wrangling for microRNAs provokes much crosstalk

Regulated expression of coding and noncoding molecules transcribed from eukaryotic genomes is essential for the differentiation, maintenance and survival of the hundreds of different cell types that constitute a complex multicellular organism. This spatiotemporal regulation of transcript levels requires crosstalk between the genome and its diverse protein and RNA products. Post-transcriptional regulation of gene expression is mediated, in part, by microRNAs (a class of small noncoding RNAs, generally 21 to 25 nucleotides in length), which modulate the transcript levels of thousands of mammalian genes. Mature microRNAs are incorporated into the RNA-induced silencing complex and recognize partially complementary sequence motifs, termed microRNA response elements (MREs), mainly in their target transcripts' 3' untranslated regions (3' UTRs). This in turn limits target expression levels, usually by repressing protein translation or by mRNA degradation [1].Four studies [2-5] recently published in Cell show how one transcript can indirectly modulate the cellular abundance of others by affecting the availability of one or more microRNAs (Table 1). Such trans-acting, microRNA-dependent properties of transcripts may form the basis of functional networks that involve large numbers of genes.A single microRNA has the potential to lower the levels of many transcripts, and target recognition is thought to decrease microRNA concentration. This suggests that transcripts sharing MREs co-regulate each other through competitive microRNA binding [6]. The first evidence for crosstalk between endogenous RNAs sharing MREs was found in plants. In Arabidopsis thaliana, a non-protein coding transcript, IPS1 (INDUCED BY PHOSPHATE STARVATION1), and a microRNA, miR-399, are induced following phosphorous starvation. The IPS1 transcript contains a conserved MRE for miR-399, which sequesters the microRNA, thereby releasing PHOS2, a protein-coding gene involved in phosphorous response, from its post