Shown are the deep cerebellar nuclei (aCc), the corpus callosum (dCf), and a transversal section of the spinal cord (gCm); kCm shows the fine detail boxed in gCi. significantly into the spines upon activation of glutamergic receptors, suggesting that these mRNPs are translationally triggered and contribute to the controlled local protein synthesis. Intro Translational silencing can determine one of several pathways for the messenger Benzyl isothiocyanate RNP (mRNP): 1st, the mRNP can be kept silent until it is eventually reactivated for translation, mRNA storage. This pathway is particularly well analyzed in the early developmental stages of insect or amphibian oocytes (Seydoux, 1996). In this case, mRNA silencing is usually achieved by shortening the poly(A) tail to a critical length that no longer supports translation initiation. Activation of the mRNA consequently involves lengthening of the poly(A) tail in a process that is usually referred to as cytoplasmic polyadenylation. In vertebrates, this process requires a characteristic, uridine-rich cytoplasmic polyadenylation element in vicinity to the 3 end of the mRNA. Cytoplasmic polyadenylation elements are recognized by the cytoplasmic polyadenylation element binding (CPEB) protein, the binding of which causes an inhibition of cap-dependent translation. After a critical phosphorylation, CPEB recruits the cytoplasmic polyadenylation machinery to the mRNA and thereby activates translation (Mendez and Richter, 2001). Another example of mRNA storage is the evolutionarily conserved translational shutdown Benzyl isothiocyanate Rabbit Polyclonal to EDG3 that occurs in response to cellular stress: the respective signaling cascades cause phosphorylation of the translation initiation factor eIF2, which blocks translation initiation of most mRNAs at the 48S pretranslational complex (Anderson Benzyl isothiocyanate and Kedersha, 2002). Second, the silenced mRNPs can be transported to subcellular compartments, to be translated Benzyl isothiocyanate there. Local protein synthesis is very important in polarized cells, as it is crucial for the maintenance of the specialized functions in the respective compartments. This is best exemplified by the neuronal axons and dendrites: in the growing axons, local translation plays a crucial role in pathfinding (Piper and Holt, 2004) and is therefore indispensable for the establishing Benzyl isothiocyanate of the proper connections in the nervous system. In the dendrites, synaptic activation causes a shift of mRNP components (Steward and Schuman, 2003; Martin and Zukin, 2006; Ferrari et al., 2007) and ribosomes (Ostroff et al., 2002) into the dendritic spines, where translation is usually activated. The encoded proteins help to modulate the synaptic strength in response to the activation, which is the molecular basis of learning and memory. Several proteins have been associated with dendritic mRNAs and implicated in their transport, among them the zip-code binding protein ZBP1 (Zhang et al., 2001), the Fragile X mental retardation protein FMRP (Bagni and Greenough, 2005), and Staufen (K?hrmann et al., 1999; Villac et al., 2004). Despite this knowledge, the process of selection of dendritic mRNAs and their transport into the dendrites remains largely enigmatic. Finally, the silenced mRNA can be degraded. Regulated mRNA degradation frequently starts with deadenylation, either through consecutive shortening of the poly(A) tail or by an endonucleolytic cleavage in the 3 UTR. Deadenylation at the 3 terminus then causes decapping at the 5 end and 53 exonucleolytic degradation (Meyer et al., 2004). In addition to the decapping enzyme and the exonuclease, the process requires the activity of several auxiliary factors, such as the seven LSm proteins, LSm1C7. The LSm proteins associate with the mRNAs that are targeted for degradation (Tharun and Parker, 2001) and are required for efficient decapping in yeast (Tharun et al., 2000). In mammals, the LSm proteins take action upstream of the degrading enzymes (Cougot et al., 2004; Andrei et al., 2005) and are probably involved in translational silencing before degradation (the LSm1-associated factor Pat1p inhibits translation in yeast [Coller and Parker, 2005]). The LSm (Like Sm) proteins take their name from a sequence homology to the Sm proteins that.
