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

Research output: Contribution to journalArticle

76 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)43-53
Number of pages11
JournalGenes and Development
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

RNA-Binding Proteins
RNA
Messenger RNA
Heterogeneous-Nuclear Ribonucleoprotein K
Actins
Carrier Proteins
Binding Sites
neurabin

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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 D.; 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 journalArticle

Patel, VL, Mitra, S, Harris, R, Buxbaum, AR, Lionnet, T, Brenowitz, MD, Girvin, M, Levy, M, Almo, SC, Singer, RH & Chao, JA 2012, 'Spatial arrangement of an RNA zipcode identifies mRNAs under post-transcriptional control', Genes and Development, vol. 26, no. 1, pp. 43-53. https://doi.org/10.1101/gad.177428.111
Patel, Vivek L. ; Mitra, Somdeb ; Harris, Richard ; Buxbaum, Adina R. ; Lionnet, Timothée ; Brenowitz, Michael D. ; Girvin, Mark ; Levy, Matthew ; Almo, Steven C. ; Singer, Robert H. ; Chao, Jeffrey A. / Spatial arrangement of an RNA zipcode identifies mRNAs under post-transcriptional control. In: Genes and Development. 2012 ; Vol. 26, No. 1. pp. 43-53.
@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 Brenowitz, {Michael D.} and Mark Girvin and Matthew Levy and Almo, {Steven C.} and Singer, {Robert H.} and Chao, {Jeffrey A.}",
year = "2012",
month = "1",
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 D.

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

VL - 26

SP - 43

EP - 53

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 1

ER -