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Title: Perinuclear localisation of cellular retinoic acid binding protein I mRNA

Abstract

Retinoids are important metabolic and developmental regulators that act through nuclear receptors. The cellular retinoic acid binding protein CRABPI has been suggested to play a role in trafficking of retinoic acid but its exact functions and subcellular localisation remain unclear. Here we show that in CHO cells both exogenous CRABPI transcripts and tagged CRABPI protein have a perinuclear distribution that depends upon the 3'UTR of the mRNA. The CRABPI 3'UTR conferred perinuclear localisation on globin reporter transcripts. Deletion analysis indicated that First 123nt of CRABPI 3'UTR are necessary for localisation of both CRABPI mRNA and protein. We propose that CRABPI mRNA is localised by a signal within its 3'UTR and that this partly determines the distribution of CRABPI protein.

Authors:
 [1];  [1];  [1];  [1];  [2]
  1. Institute for Cell and Molecular Biosciences, University of Newcastle, Newcastle-upon-Tyne NE2 4HH (United Kingdom)
  2. Institute for Cell and Molecular Biosciences, University of Newcastle, Newcastle-upon-Tyne NE2 4HH (United Kingdom). E-mail: j.e.hesketh@ncl.ac.uk
Publication Date:
OSTI Identifier:
20798788
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 340; Journal Issue: 1; Other Information: DOI: 10.1016/j.bbrc.2005.12.006; PII: S0006-291X(05)02732-4; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARBOXYLIC ACIDS; CHO CELLS; GLOBINS; MESSENGER-RNA; RECEPTORS; RETINOIC ACID; SIGNALS

Citation Formats

Levadoux-Martin, M., Li, Y., Blackburn, A., Chabanon, H., and Hesketh, J.E. Perinuclear localisation of cellular retinoic acid binding protein I mRNA. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2005.12.006.
Levadoux-Martin, M., Li, Y., Blackburn, A., Chabanon, H., & Hesketh, J.E. Perinuclear localisation of cellular retinoic acid binding protein I mRNA. United States. doi:10.1016/j.bbrc.2005.12.006.
Levadoux-Martin, M., Li, Y., Blackburn, A., Chabanon, H., and Hesketh, J.E. Fri . "Perinuclear localisation of cellular retinoic acid binding protein I mRNA". United States. doi:10.1016/j.bbrc.2005.12.006.
@article{osti_20798788,
title = {Perinuclear localisation of cellular retinoic acid binding protein I mRNA},
author = {Levadoux-Martin, M. and Li, Y. and Blackburn, A. and Chabanon, H. and Hesketh, J.E.},
abstractNote = {Retinoids are important metabolic and developmental regulators that act through nuclear receptors. The cellular retinoic acid binding protein CRABPI has been suggested to play a role in trafficking of retinoic acid but its exact functions and subcellular localisation remain unclear. Here we show that in CHO cells both exogenous CRABPI transcripts and tagged CRABPI protein have a perinuclear distribution that depends upon the 3'UTR of the mRNA. The CRABPI 3'UTR conferred perinuclear localisation on globin reporter transcripts. Deletion analysis indicated that First 123nt of CRABPI 3'UTR are necessary for localisation of both CRABPI mRNA and protein. We propose that CRABPI mRNA is localised by a signal within its 3'UTR and that this partly determines the distribution of CRABPI protein.},
doi = {10.1016/j.bbrc.2005.12.006},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 340,
place = {United States},
year = {Fri Feb 03 00:00:00 EST 2006},
month = {Fri Feb 03 00:00:00 EST 2006}
}
  • The structural integrity of cellular retinoic acid-binding protein II (CRABPII) has been investigated using the crystal structures of CRABPII mutants. The overall fold was well maintained by these CRABPII mutants, each of which carried multiple different mutations. A water-mediated network is found to be present across the large binding cavity, extending from Arg111 deep inside the cavity to the {alpha} 2 helix at its entrance. This chain of interactions acts as a 'pillar' that maintains the integrity of the protein. The disruption of the water network upon loss of Arg111 leads to decreased structural integrity of the protein. A water-mediatedmore » network can be re-established by introducing the hydrophilic Glu121 inside the cavity, which results in a rigid protein with the {alpha}2 helix adopting an altered conformation compared with wild-type CRABPII.« less
  • A water network stabilizes the structure of cellular retionic acid binding protein II. The structural integrity of cellular retinoic acid-binding protein II (CRABPII) has been investigated using the crystal structures of CRABPII mutants. The overall fold was well maintained by these CRABPII mutants, each of which carried multiple different mutations. A water-mediated network is found to be present across the large binding cavity, extending from Arg111 deep inside the cavity to the α2 helix at its entrance. This chain of interactions acts as a ‘pillar’ that maintains the integrity of the protein. The disruption of the water network upon lossmore » of Arg111 leads to decreased structural integrity of the protein. A water-mediated network can be re-established by introducing the hydrophilic Glu121 inside the cavity, which results in a rigid protein with the α2 helix adopting an altered conformation compared with wild-type CRABPII.« less
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