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She2p is an RNA-binding protein that recognizes a zipcode on specific mRNAs necessary for the assembly of a protein complex that localizes them to the yeast bud tip. In this issue of Genes & Development, Shen and colleagues (pp. 1914-1926) demonstrate that She2p associates with RNAPII globally, but then recognizes the nascent chain only if it contains a zipcode. This demonstrates yet another case where the mRNA's cytoplasmic fate is determined by the RNAPII complex. [ABSTRACT FROM AUTHOR]

ZBP1 (zipcode binding protein 1) is an RNA-binding protein involved in many posttranscriptional processes, such as RNA localization, RNA stability, and translational control. ZBP1 is abundantly expressed in embryonic development, but its expression is silenced in most adult tissues. Reactivation of the ZBP1 gene has been reported in various human tumors. In this study, we identified a detailed molecular mechanism of ZBP1 transactivation in breast cancer cells. We show that β-catenin, a protein that functions in both cell adhesion and transcription, specifically binds to the ZBP1 promoter via a conserved β-catenin/TCF4 response element and activates its gene expression. ZBP1 activation is also closely correlated with nuclear translocation of β-catenin in human breast tumors. We further demonstrate feedback regulation by finding that ZBP1 physically associates with β-catenin mRNA in vivo and increases its stability. These experiments suggest that in breast cancer cells, the expression of ZBP1 and the expression of β-catenin are coordinately regulated. β-Catenin mediates the transcription of the ZBP1 gene, while ZBP1 promotes the stability of β-catenin mRNA. [ABSTRACT FROM AUTHOR]

After the export from the nucleus it turns out that all mRNAs are not treated equally. Not only is mRNA subject to translation, but also through RNA-binding proteins and other trans-acting factors, eukaryotic cells interpret codes for spatial sorting within the mRNA sequence. These codes instruct the cytoskeleton and translation apparatus to make decisions about where to transport and when to translate the intended protein product. Signaling pathways decode extra-cellular cues and can modify transport and translation factors in the appropriate cytoplasmic space to achieve translation locally. Identifying regulatory sites on transport factors as well as novel physiological functions for well-known translation factors has provided significant advances in how spatially controlled translation impacts cell function. [Copyright &y& Elsevier]

How RNA-binding proteins recognize specific sets of target mRNAs remains poorly understood because current approaches depend primarily on sequence information. In this study, we demonstrate that specific recognition of messenger RNAs (mRNAs) by RNA-binding proteins requires the correct spatial positioning of these sequences. We characterized both the cis-acting sequence elements and the spatial restraints that define the mode of RNA binding of the zipcode-binding protein 1 (ZBP1/IMP1/IGF2BP1) to the β-actin zipcode. The third and fourth KH (hnRNP K homology) domains of ZBP1 specifically recognize a bipartite RNA element comprised of a 5' element (CGGAC) followed by a variable 3' element (C/A-CA-C/U) that must be appropriately spaced. Remarkably, the orientation of these elements is interchangeable within target transcripts bound by ZBP1. The spatial relationship of this consensus binding site identified conserved transcripts that were verified to associate with ZBP1 in vivo. The dendritic localization of one of these transcripts, spinophilin, was found to be dependent on both ZBP1 and the RNA elements recognized by ZBP1 KH34. [ABSTRACT FROM AUTHOR]