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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2007.05.028 Byline: Corinna Giorgi (1), Gene W. Yeo (2), Martha E. Stone (3), Donald B. Katz (3), Christopher Burge (4), Gina Turrigiano (5), Melissa J. Moore (1) Abstract: Proper neuronal function and several forms of synaptic plasticity are highly dependent on precise control of mRNA translation, particularly in dendrites. We find that eIF4AIII, a core exon junction complex (EJC) component loaded onto mRNAs by pre-mRNA splicing, is associated with neuronal mRNA granules and dendritic mRNAs. eIF4AIII knockdown markedly increases both synaptic strength and GLUR1 AMPA receptor abundance at synapses. eIF4AIII depletion also increases ARC, a protein required for maintenance of long-term potentiation; arc mRNA, one of the most abundant in dendrites, is a natural target for nonsense-mediated decay (NMD). Numerous new NMD candidates, some with potential to affect synaptic activity, were also identified computationally. Two models are presented for how translation-dependent decay pathways such as NMD might advantageously function as critical brakes for protein synthesis in cells such as neurons that are highly dependent on spatially and temporally restricted protein expression. Author Affiliation: (1) Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, USA (2) Crick-Jacobs Center for Computational and Theoretical Biology Salk Institute, La Jolla, CA 92037, USA (3) Department of Psychology and Volen Center for Complex Systems, Brandeis University, Waltham, MA 02454, USA (4) Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA (5) Department of Biology and Volen Center for Complex Systems, Brandeis University, Waltham, MA 02454, USA Article History: Received 12 July 2006; Revised 23 December 2006; Accepted 9 May 2007 Article Note: (miscellaneous) Published: July 12, 2007

The author reviews the publications on the mechanisms and regulation of nuclear RNA decay. The topics of interest include RNA turnover in mammalian cells, the nuclear decay pathways and the interplay between the RNA processing and decay machineries.

The pathway from gene activation in the nucleus to mRNA translation and decay at specific locations in the cytoplasm is both streamlined and highly interconnected. This review discusses how pre-mRNA processing, including 5' cap addition, splicing, and polyadenylation, contributes to both the efficiency and fidelity of gene expression. The connections of pre-mRNA processing to upstream events in transcription and downstream events, including translation and mRNA decay, are elaborate, extensive, and remarkably interwoven.