BBB seminar: Melissa J. Moore
mRNAs with a complex: the long-term consequences of a nuclear upbringing
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Melissa J. Moore
Department of Biochemistry and Molecular Pharmacology, Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA, USA
From yeast to mammals, it is now clear that the nuclear “history” of a messenger RNA is crucial for determining its downstream fate. mRNA localization, translation and stability in the cytoplasm are often pre-destined in the nucleus, directed by the composition and architecture of nuclear assembled mRNA-protein (mRNP) complexes. One set of mRNP proteins, the exon junction complex (EJC), is deposited on mRNAs as a consequence of pre-mRNA splicing in the nucleus and removed only upon mRNA translation in the cytoplasm. Functionally, the EJC has been implicated in mRNA localization, translational efficiency and as an enhancer of nonsense-mediated mRNA decay (NMD). As the newest addition to this list, we recently described a key role for the EJC in limiting protein expression, and thereby synaptic strength, in mammalian neurons. One clear EJC function in neurons is as an initiator of translation-dependent decay (TDD) of Arc mRNA (Giorgi et al. , Cell, 2007, 130:179-91). Possible connections to other TDD pathways will be discussed, as well as the broader implications for such RNA decay pathways in the general regulation of eukaryotic gene expression.
Host: Anni Vedeler <anni.vedeler@biomed.uib.no>, Department of Biomedicine