|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 50, 47338-47351, December 14, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Departments of Mammalian apolipoprotein B (apoB) mRNA
editing is mediated by a multicomponent holoenzyme containing apobec-1
and ACF. We have now identified CUGBP2, a 54-kDa RNA-binding protein,
as a component of this holoenzyme. CUGBP2 and ACF co-fractionate in bovine liver S-100 extracts, and addition of recombinant apobec-1 leads
to assembly of a holoenzyme. Immunodepletion of CUGBP2 co-precipitates ACF, and these proteins co-localize the nucleus of transfected cells,
suggesting that CUGBP2 and ACF are bound in vivo. CUGBP2 binds apoB RNA, specifically an AU-rich sequence located immediately upstream of the edited cytidine. ApoB RNA from McA cells, bound to
CUGBP2, was more extensively edited than the unbound fraction. However,
addition of recombinant CUGBP2 to a reconstituted system demonstrated a
dose-dependent inhibition of C to U RNA editing, which was
rescued with either apobec-1 or ACF. Antisense CUGBP2 knockout
increased endogenous apoB RNA editing, whereas antisense knockout of
either apobec-1 or ACF expression eliminated apoB RNA editing,
establishing the absolute requirement of these components of the core
enzyme. These data suggest that CUGBP2 plays a role in apoB mRNA
editing by forming a regulatory complex with the three components of
the minimal editing enzyme, apobec-1, ACF, and apoB RNA.
Novel Role for RNA-binding Protein CUGBP2 in
Mammalian RNA Editing
CUGBP2 MODULATES C TO U EDITING OF APOLIPOPROTEIN B mRNA BY
INTERACTING WITH APOBEC-1 AND ACF, THE APOBEC-1 COMPLEMENTATION
FACTOR*
§¶,¶,,
,,, and**
Internal Medicine and
** Pharmacology and Molecular Biology, Washington University
Medical School, Saint Louis, Missouri 63110 and the Medical
Research Council Molecular Medicine Group, Clinical Sciences
Center, Imperial College School of Medicine, Hammersmith Hospital,
London W12 0NN, United Kingdom
*
This work was supported by National Institutes of Health
Grants HL38180 and DK56260 (to N. O. D.), National Institutes of Health Digestive Disease Research Core Center Grant DK52574
(N. O. D.), a Pilot and Feasibility Award from National Institutes of
Health Digestive Disease Core Center (to S. A.), and the
American Gastroenterology Association/American Digestive Health
Foundation Research Scholars Award (to S. A.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence may be addressed: Washington
University School of Medicine, Dept. of Internal Medicine, Div. of
Gastroenterology, Campus Box 8124, 660 South Euclid Ave., St. Louis, MO
63110. Tel.: 314-362-2027; Fax: 314-362-2033; E-mail:
nod@im.wustl.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Ramalingam, G. Natarajan, C. Schafer, D. Subramaniam, R. May, I. Ramachandran, L. Queimado, C. W. Houchen, and S. Anant Novel intestinal splice variants of RNA-binding protein CUGBP2: isoform-specific effects on mitotic catastrophe Am J Physiol Gastrointest Liver Physiol, April 1, 2008; 294(4): G971 - G981. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Chapple, K. Anthony, T. R. Martin, A. Dev, T. A. Cooper, and J.-M. Gallo Expression, localization and tau exon 10 splicing activity of the brain RNA-binding protein TNRC4 Hum. Mol. Genet., November 15, 2007; 16(22): 2760 - 2769. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Chen, T. L. Eggerman, and A. P. Patterson ApoB mRNA editing is mediated by a coordinated modulation of multiple apoB mRNA editing enzyme components Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G53 - G65. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Blanc, J. O. Henderson, E. P. Newberry, S. Kennedy, J. Luo, and N. O. Davidson Targeted Deletion of the Murine apobec-1 Complementation Factor (acf) Gene Results in Embryonic Lethality Mol. Cell. Biol., August 15, 2005; 25(16): 7260 - 7269. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Crooke, M. J. Graham, K. M. Lemonidis, C. P. Whipple, S. Koo, and R. J. Perera An apolipoprotein B antisense oligonucleotide lowers LDL cholesterol in hyperlipidemic mice without causing hepatic steatosis J. Lipid Res., May 1, 2005; 46(5): 872 - 884. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Faustino and T. A. Cooper Identification of Putative New Splicing Targets for ETR-3 Using Sequences Identified by Systematic Evolution of Ligands by Exponential Enrichment Mol. Cell. Biol., February 1, 2005; 25(3): 879 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. Ladd and T. A. Cooper Multiple domains control the subcellular localization and activity of ETR-3, a regulator of nuclear and cytoplasmic RNA processing events J. Cell Sci., July 15, 2004; 117(16): 3519 - 3529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Donnini, A. Lapucci, L. Papucci, E. Witort, A. Jacquier, G. Brewer, A. Nicolin, S. Capaccioli, and N. Schiavone Identification of TINO: A NEW EVOLUTIONARILY CONSERVED BCL-2 AU-RICH ELEMENT RNA-BINDING PROTEIN J. Biol. Chem., May 7, 2004; 279(19): 20154 - 20166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Suspene, P. Sommer, M. Henry, S. Ferris, D. Guetard, S. Pochet, A. Chester, N. Navaratnam, S. Wain-Hobson, and J.-P. Vartanian APOBEC3G is a single-stranded DNA cytidine deaminase and functions independently of HIV reverse transcriptase Nucleic Acids Res., April 30, 2004; 32(8): 2421 - 2429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Ladd, N. H. Nguyen, K. Malhotra, and T. A. Cooper CELF6, a Member of the CELF Family of RNA-binding Proteins, Regulates Muscle-specific Splicing Enhancer-dependent Alternative Splicing J. Biol. Chem., April 23, 2004; 279(17): 17756 - 17764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Sowden, D. M. Lehmann, X. Lin, C. O. Smith, and H. C. Smith Identification of Novel Alternative Splice Variants of APOBEC-1 Complementation Factor with Different Capacities to Support Apolipoprotein B mRNA Editing J. Biol. Chem., January 2, 2004; 279(1): 197 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P. Lau and L. Chan Involvement of a Chaperone Regulator, Bcl2-associated Athanogene-4, in Apolipoprotein B mRNA Editing J. Biol. Chem., December 26, 2003; 278(52): 52988 - 52996. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Blanc, S. Kennedy, and N. O. Davidson A Novel Nuclear Localization Signal in the Auxiliary Domain of Apobec-1 Complementation Factor Regulates Nucleocytoplasmic Import and Shuttling J. Biol. Chem., October 17, 2003; 278(42): 41198 - 41204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Cok, S. J. Acton, and A. R. Morrison The Proximal Region of the 3'-Untranslated Region of Cyclooxygenase-2 is Recognized by a Multimeric Protein Complex Containing HuR, TIA-1, TIAR, and the Heterogeneous Nuclear Ribonucleoprotein U J. Biol. Chem., September 19, 2003; 278(38): 36157 - 36162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mukhopadhyay, M. Plateroti, S. Anant, F. Nassir, J. Samarut, and N. O. Davidson Thyroid Hormone Regulates Hepatic Triglyceride Mobilization and Apolipoprotein B Messenger Ribonucleic Acid Editing in a Murine Model of Congenital Hypothyroidism Endocrinology, February 1, 2003; 144(2): 711 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Blanc and N. O. Davidson C-to-U RNA Editing: Mechanisms Leading to Genetic Diversity J. Biol. Chem., January 10, 2003; 278(3): 1395 - 1398. [Full Text] [PDF]
|
|
|
|
|
|
H. Lellek, S. Welker, I. Diehl, R. Kirsten, and J. Greeve Reconstitution of mRNA Editing in Yeast Using a Gal4-ApoB-Gal80 Fusion Transcript as the Selectable Marker J. Biol. Chem., June 21, 2002; 277(26): 23638 - 23644. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |