In a tight spot: ARE-mRNAs at processing bodies (original) (raw)

  1. Georg Stoecklin1 and
  2. Paul Anderson2,3
  3. 1 German Cancer Research Center, 69120 Heidelberg, Germany;
  4. 2 Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

Compartimentalization of proteins and nucleic acids within nuclear and cytoplasmic domains is essential for many cellular functions (Spector 2006). Although biochemical analysis of cellular lysates has provided important information about the processes of mRNA translation and decay, recent results showing that these events occur at discrete cytoplasmic RNA granules (Anderson and Kedersha 2006) makes it essential that we understand the contribution of subcellular localization to these basic mechanisms. In this issue of Genes & Development, Franks and Lykke-Andersen (2007) describe the importance of cytoplasmic processing bodies (PBs) in regulating the translation and decay of a class of mRNAs bearing an adenine/uridine-rich destabilizing element. Their studies provide important new insights into the link between mRNA translation and decay by revealing the role that RNA granules play in these processes.

As and Us mark short-lived mRNAs

In 1986, a highly conserved sequence motif composed of adenosine and uridine residues caught the eye of a group of scientists who were analyzing newly cloned cytokine cDNAs. The adenine/uridine-rich elements (AREs) found in the 3′ untranslated regions (UTRs) of these transcripts were predicted to regulate some aspect of mRNA metabolism (Caput et al. 1986). In that same year, an ARE was shown to cause the rapid degradation of mRNA encoding granulocyte macrophage-colony-stimulating factor (GM-CSF) (Shaw and Kamen 1986). In ensuing years, it has become clear that ARE-mediated decay (AMD) is a common mechanism that may regulate the expression of up to 5%–8% of all mRNAs (Bakheet et al. 2006). Several groups identified proteins that bind to AREs, but a breakthrough was made unexpectedly by scientists studying a putative transcription factor known as tristetraprolin (TTP or ZFP36). Mutant mice lacking TTP showed signs of severe generalized inflammation, a phenotype that was caused by overproduction of tumor necrosis factor-α (TNFα) (Carballo et al. 1998). Surprisingly, the transcription rate of TNFα was normal …