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

Vivek L. Patel, Somdeb Mitra, Richard Harris, Adina R. Buxbaum, Timothée Lionnet, Michael Brenowitz, Mark E. Girvin, Matthew Levy, Steven C. Almo, Robert H. Singer, Jeffrey A. Chao

Research output: Contribution to journalArticlepeer-review

104 Scopus citations


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 b-actin zipcode. The third and fourth KH (hnRNP K homology) domains of ZBP1 specifically recognize a bipartite RNA element comprised of a 59 element (CGGAC) followed by a variable 39 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.

Original languageEnglish (US)
Pages (from-to)43-53
Number of pages11
JournalGenes and Development
Issue number1
StatePublished - Jan 1 2012


  • KH domain
  • RNA localization
  • RNA-binding protein
  • ZBP1

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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