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Publication : Spatial arrangement of an RNA zipcode identifies mRNAs under post-transcriptional control.

First Author  Patel VL Year  2012
Journal  Genes Dev Volume  26
Issue  1 Pages  43-53
PubMed ID  22215810 Mgi Jnum  J:179370
Mgi Id  MGI:5302130 Doi  10.1101/gad.177428.111
Citation  Patel VL, et al. (2012) Spatial arrangement of an RNA zipcode identifies mRNAs under post-transcriptional control. Genes Dev 26(1):43-53
abstractText  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 beta-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.
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