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

Research output: Contribution to journal › Article › peer-review

89 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

Keywords

KH domain
RNA localization
RNA-binding protein
ZBP1

ASJC Scopus subject areas

Genetics
Developmental Biology

Access to Document

10.1101/gad.177428.111

Fingerprint Dive into the research topics of 'Spatial arrangement of an RNA zipcode identifies mRNAs under post-transcriptional control'. Together they form a unique fingerprint.

Cite this

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 › peer-review

@article{401350aedc694bc384651fc3c283811a,

title = "Spatial arrangement of an RNA zipcode identifies mRNAs under post-transcriptional control",

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.",

keywords = "KH domain, RNA localization, RNA-binding protein, ZBP1",

author = "Patel, {Vivek L.} and Somdeb Mitra and Richard Harris and Buxbaum, {Adina R.} and Timoth{\'e}e Lionnet and Michael Brenowitz and Mark Girvin and Matthew Levy and Almo, {Steven C.} and Singer, {Robert H.} and Chao, {Jeffrey A.}",

year = "2012",

month = jan,

day = "1",

doi = "10.1101/gad.177428.111",

language = "English (US)",

volume = "26",

pages = "43--53",

journal = "Genes and Development",

issn = "0890-9369",

publisher = "Cold Spring Harbor Laboratory Press",

number = "1",

}

TY - JOUR

T1 - Spatial arrangement of an RNA zipcode identifies mRNAs under post-transcriptional control

AU - Patel, Vivek L.

AU - Mitra, Somdeb

AU - Harris, Richard

AU - Buxbaum, Adina R.

AU - Lionnet, Timothée

AU - Brenowitz, Michael

AU - Girvin, Mark

AU - Levy, Matthew

AU - Almo, Steven C.

AU - Singer, Robert H.

AU - Chao, Jeffrey A.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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.

AB - 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.

KW - KH domain

KW - RNA localization

KW - RNA-binding protein

KW - ZBP1

UR - http://www.scopus.com/inward/record.url?scp=84855302804&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855302804&partnerID=8YFLogxK

U2 - 10.1101/gad.177428.111

DO - 10.1101/gad.177428.111

M3 - Article

C2 - 22215810

AN - SCOPUS:84855302804

VL - 26

SP - 43

EP - 53

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 1

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Cite this