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 Girvin; Matthew Levy; Steven C. Almo; Robert H. Singer; Jeffrey A. Chao

doi:10.1101/gad.177428.111

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 Girvin, Matthew Levy, Steven C. Almo, Robert H. Singer, Jeffrey A. Chao

Biochemistry

Research output: Contribution to journal › Article

82 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	43-53
Number of pages	11
Journal	Genes and Development
Volume	26
Issue number	1
DOIs	https://doi.org/10.1101/gad.177428.111
State	Published - Jan 1 2012

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Keywords

KH domain
RNA localization
RNA-binding protein
ZBP1

ASJC Scopus subject areas

Genetics
Developmental Biology

Cite this

Patel, V. L., Mitra, S., Harris, R., Buxbaum, A. R., Lionnet, T., Brenowitz, M., Girvin, M., Levy, M., Almo, S. C., Singer, R. H., & Chao, J. A. (2012). Spatial arrangement of an RNA zipcode identifies mRNAs under post-transcriptional control. Genes and Development, 26(1), 43-53. https://doi.org/10.1101/gad.177428.111

Spatial arrangement of an RNA zipcode identifies mRNAs under post-transcriptional control. / Patel, Vivek L.; Mitra, Somdeb; Harris, Richard; Buxbaum, Adina R.; Lionnet, Timothée; Brenowitz, Michael; Girvin, Mark; Levy, Matthew; Almo, Steven C.; Singer, Robert H.; Chao, Jeffrey A.

In: Genes and Development, Vol. 26, No. 1, 01.01.2012, p. 43-53.

Research output: Contribution to journal › Article

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10.1101/gad.177428.111