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Molecular and Cellular Biology, July 2000, p. 4572-4579, Vol. 20, No. 13
Laboratoire de Pharmacologie
Expérimentale, Université Catholique de Louvain, UCL
54.10, B-1200 Brussels,1 and
Département de Biologie Moléculaire, Laboratoire de
Chimie Biologique, Université Libre de Bruxelles, B-1640
Rhodes-Saint-Genèse,2 Belgium
Received 10 December 1999/Returned for modification 1 February
2000/Accepted 5 April 2000
The alternative polyadenylation of the mRNA encoding the amyloid
precursor protein (APP) involved in Alzheimer's disease generates two
molecules, with the first of these containing 258 additional nucleotides in the 3' untranslated region (3'UTR). We have previously shown that these 258 nucleotides increase the translation of APP mRNA
injected in Xenopus oocytes (5). Here, we
demonstrate that this mechanism occurs in CHO cells as well. We also
present evidence that the 3'UTR containing 8 nucleotides more than the
short 3'UTR allows the recovery of an efficiency of translation similar
to that of the long 3'UTR. Moreover, the two guanine residues located at the 3' ends of these 8 nucleotides play a key role in the
translational control. Using gel retardation mobility shift assay, we
show that proteins from Xenopus oocytes, CHO cells, and
human brain specifically bind to the short 3'UTR but not to the long
one. The two guanine residues involved in the translational control
inhibit this specific binding by 65%. These results indicate that
there is a correlation between the binding of proteins to the 3'UTR of
APP mRNA and the efficiency of mRNA translation, and that a GG motif
controls both binding of proteins and translation.
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
A GG Nucleotide Sequence of the 3' Untranslated
Region of Amyloid Precursor Protein mRNA Plays a Key Role in the
Regulation of Translation and the Binding of Proteins
*
Corresponding author. Mailing address: Laboratoire de
Pharmacologie Expérimentale, Université Catholique de
Louvain, UCL 54.10, Avenue Hipppocrate 54, B-1200 Brussels, Belgium.
Phone: 32 2 764 93 41. Fax: 32 2 764 93 40. E-mail:
Octave{at}nchm.ucl.ac.be.
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