Turnover in the Alps: an mRNA perspective

Abstract

The EMBO Workshop on Mechanisms and Regulation of mRNA Turnover took place in the remote mountain valley of Arolla, Switzerland, from 28 August to 1 September 2005. The workshop was organized by C. Clayton, W. Filipowizc, R. Gherzi and C. Moroni, and was supported by EMBO, the Kontaktgruppe fur Forschungsfragen (Ciba Spezialitatenchemie, Roche, Novartis, Serono and Syngenta), and the Swiss National Science Foundation. ![][1] The control of messenger RNA turnover is increasingly being recognized as having a crucial role in the regulation of gene expression (Wilusz & Wilusz, 2004). The stability of mRNAs is known to vary during development and also in response to environmental factors, such as cell stress and pro‐inflammatory stimuli. Once exported from the nucleus, most mRNAs are relatively stable in the cytoplasm (with half‐lives >10 h in mammalian cells); however, a subset of mRNAs decays rapidly (with half‐lives between 15 min and 2 h). The rapid decay of these mRNAs is determined by specific destabilizing elements, the most widespread of which is a heterogeneous group of AU‐rich elements (AREs) located in the 3′ untranslated region (UTR) of an estimated 8% of all mRNAs (Khabar, 2005). ARE‐mediated mRNA decay (AMD; Fig 1A) requires a set of RNA‐binding proteins that recognize the ARE and target the mRNA to the basic decay machinery (Fig 1C). As many ARE‐containing mRNAs encode proteins involved in inflammation, AMD can be viewed as a ‘post‐transcriptional operon’ (Keene & Tenenbaum, 2002), a term that refers to the general observation that RNA‐binding proteins tend to coordinately regulate groups of mRNAs that encode proteins with a common function. Figure 1. General scheme of messenger RNA decay pathways. ( A ) The regulation of gene expression involves the control of mRNA degradation at the post‐transcriptional level. mRNAs containing an AU‐rich element (ARE) in their 3′ untranslated region (UTR) undergo rapid ARE‐mediated mRNA … [1]: /embed/graphic-1.gif