2′,3′-cyclic nucleotide 3′-phosphodiesterase: A novel RNA-binding protein that inhibits protein synthesis

Michel Gravel, Francis Robert, Vicky Kottis, Imed Gallouzi, Jerry Pelletier, Peter E. Braun

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

2′,3′-Cyclic nucleotide 3′-phosphodiesterase (CNP) is one of the earliest myelin-related proteins to be specifically expressed in differentiating oligodendrocytes (ODCs) in the central nervous system (CNS) and is implicated in myelin biogenesis. CNP possesses an in vitro enzymatic activity, whose in vivo relevance remains to be defined, because substrates with 2′,3,-cyclic termini have not yet been identified. To characterize CNP function better, we previously determined the structure of the CNP catalytic domain by NMR. Interestingly, the structure is remarkably similar to the plant cyclic nucleotide phosphodiesterase (CPDase) from A. thaliana and the bacterial 2′-5′ RNA ligase from T. thermophilus, which are known to play roles in RNA metabolism. Here we show that CNP is an RNA-binding protein. Furthermore, by using precipitation analyses, we demonstrate that CNP associates with poly(A)+ mRNAs in vivo and suppresses translation in vitro in a dose-dependent manner. With SELEX, we isolated RNA aptamers that can suppress the inhibitory effect of CNP on translation. We also demonstrate that CNP1 can bridge an association between tubulin and RNA. These results suggest that CNP1 may regulate expression of mRNAs in ODCs of the CNS.

Original languageEnglish
Pages (from-to)1069-1079
Number of pages11
JournalJournal of Neuroscience Research
Volume87
Issue number5
DOIs
Publication statusPublished - 2009
Externally publishedYes

Fingerprint

RNA-Binding Proteins
Cyclic Nucleotides
Phosphoric Diester Hydrolases
Proteins
Oligodendroglia
RNA
Central Nervous System
Nucleotide Aptamers
Myelin Proteins
Messenger RNA
Tubulin
Ligases
Myelin Sheath
Catalytic Domain

Keywords

  • CNP
  • RNA binding
  • Translation repression

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

2′,3′-cyclic nucleotide 3′-phosphodiesterase : A novel RNA-binding protein that inhibits protein synthesis. / Gravel, Michel; Robert, Francis; Kottis, Vicky; Gallouzi, Imed; Pelletier, Jerry; Braun, Peter E.

In: Journal of Neuroscience Research, Vol. 87, No. 5, 2009, p. 1069-1079.

Research output: Contribution to journalArticle

Gravel, Michel ; Robert, Francis ; Kottis, Vicky ; Gallouzi, Imed ; Pelletier, Jerry ; Braun, Peter E. / 2′,3′-cyclic nucleotide 3′-phosphodiesterase : A novel RNA-binding protein that inhibits protein synthesis. In: Journal of Neuroscience Research. 2009 ; Vol. 87, No. 5. pp. 1069-1079.
@article{7bdd142c2b1d48b1a717e0ad893c73b8,
title = "2′,3′-cyclic nucleotide 3′-phosphodiesterase: A novel RNA-binding protein that inhibits protein synthesis",
abstract = "2′,3′-Cyclic nucleotide 3′-phosphodiesterase (CNP) is one of the earliest myelin-related proteins to be specifically expressed in differentiating oligodendrocytes (ODCs) in the central nervous system (CNS) and is implicated in myelin biogenesis. CNP possesses an in vitro enzymatic activity, whose in vivo relevance remains to be defined, because substrates with 2′,3,-cyclic termini have not yet been identified. To characterize CNP function better, we previously determined the structure of the CNP catalytic domain by NMR. Interestingly, the structure is remarkably similar to the plant cyclic nucleotide phosphodiesterase (CPDase) from A. thaliana and the bacterial 2′-5′ RNA ligase from T. thermophilus, which are known to play roles in RNA metabolism. Here we show that CNP is an RNA-binding protein. Furthermore, by using precipitation analyses, we demonstrate that CNP associates with poly(A)+ mRNAs in vivo and suppresses translation in vitro in a dose-dependent manner. With SELEX, we isolated RNA aptamers that can suppress the inhibitory effect of CNP on translation. We also demonstrate that CNP1 can bridge an association between tubulin and RNA. These results suggest that CNP1 may regulate expression of mRNAs in ODCs of the CNS.",
keywords = "CNP, RNA binding, Translation repression",
author = "Michel Gravel and Francis Robert and Vicky Kottis and Imed Gallouzi and Jerry Pelletier and Braun, {Peter E.}",
year = "2009",
doi = "10.1002/jnr.21939",
language = "English",
volume = "87",
pages = "1069--1079",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - 2′,3′-cyclic nucleotide 3′-phosphodiesterase

T2 - A novel RNA-binding protein that inhibits protein synthesis

AU - Gravel, Michel

AU - Robert, Francis

AU - Kottis, Vicky

AU - Gallouzi, Imed

AU - Pelletier, Jerry

AU - Braun, Peter E.

PY - 2009

Y1 - 2009

N2 - 2′,3′-Cyclic nucleotide 3′-phosphodiesterase (CNP) is one of the earliest myelin-related proteins to be specifically expressed in differentiating oligodendrocytes (ODCs) in the central nervous system (CNS) and is implicated in myelin biogenesis. CNP possesses an in vitro enzymatic activity, whose in vivo relevance remains to be defined, because substrates with 2′,3,-cyclic termini have not yet been identified. To characterize CNP function better, we previously determined the structure of the CNP catalytic domain by NMR. Interestingly, the structure is remarkably similar to the plant cyclic nucleotide phosphodiesterase (CPDase) from A. thaliana and the bacterial 2′-5′ RNA ligase from T. thermophilus, which are known to play roles in RNA metabolism. Here we show that CNP is an RNA-binding protein. Furthermore, by using precipitation analyses, we demonstrate that CNP associates with poly(A)+ mRNAs in vivo and suppresses translation in vitro in a dose-dependent manner. With SELEX, we isolated RNA aptamers that can suppress the inhibitory effect of CNP on translation. We also demonstrate that CNP1 can bridge an association between tubulin and RNA. These results suggest that CNP1 may regulate expression of mRNAs in ODCs of the CNS.

AB - 2′,3′-Cyclic nucleotide 3′-phosphodiesterase (CNP) is one of the earliest myelin-related proteins to be specifically expressed in differentiating oligodendrocytes (ODCs) in the central nervous system (CNS) and is implicated in myelin biogenesis. CNP possesses an in vitro enzymatic activity, whose in vivo relevance remains to be defined, because substrates with 2′,3,-cyclic termini have not yet been identified. To characterize CNP function better, we previously determined the structure of the CNP catalytic domain by NMR. Interestingly, the structure is remarkably similar to the plant cyclic nucleotide phosphodiesterase (CPDase) from A. thaliana and the bacterial 2′-5′ RNA ligase from T. thermophilus, which are known to play roles in RNA metabolism. Here we show that CNP is an RNA-binding protein. Furthermore, by using precipitation analyses, we demonstrate that CNP associates with poly(A)+ mRNAs in vivo and suppresses translation in vitro in a dose-dependent manner. With SELEX, we isolated RNA aptamers that can suppress the inhibitory effect of CNP on translation. We also demonstrate that CNP1 can bridge an association between tubulin and RNA. These results suggest that CNP1 may regulate expression of mRNAs in ODCs of the CNS.

KW - CNP

KW - RNA binding

KW - Translation repression

UR - http://www.scopus.com/inward/record.url?scp=65949118902&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65949118902&partnerID=8YFLogxK

U2 - 10.1002/jnr.21939

DO - 10.1002/jnr.21939

M3 - Article

C2 - 19021295

AN - SCOPUS:65949118902

VL - 87

SP - 1069

EP - 1079

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 5

ER -