Nucleic Acids Research Advance Access originally published online on April 16, 2007
Nucleic Acids Research 2007 35(9):2975-2985; doi:10.1093/nar/gkm191
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2007, Vol. 35, No. 9 2975-2985
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Complex translational regulation of BACE1 involves upstream AUGs and stimulatory elements within the 5' untranslated region
1San Raffaele Scientific Institute, via Olgettina 58, 20132 Milano, Italy, 2Vita-Salute San Raffaele University, via Olgettina 58, I-20132 Milano, Italy, 3European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany, 4Italian Institute of Technology (IIT), Research Unit of Molecular Neuroscience, via Olgettina 58, I-20132 Milano, Italy and 5Istituto Nazionale di Neuroscienze, via Olgettina 58, I-20132 Milano, Italy
*To whom correspondence should be addressed. Tel: +39-02-2643-4817; Fax: +39-02-2643-4813; Email: zacchetti.daniele{at}hsr.it
Received February 12, 2007. Revised March 16, 2007. Accepted March 16, 2007.
BACE1 is the protease responsible for the production of amyloid-ß peptides that accumulate in the brain of Alzheimer's disease (AD) patients. BACE1 expression is regulated at the transcriptional, as well as post-transcriptional level. Very high BACE1 mRNA levels have been observed in pancreas, but the protein and activity were found mainly in brain. An up-regulation of the protein has been described in some AD patients without a change in transcript levels. The features of BACE1 5' untranslated region (5' UTR), such as the length, GC content, evolutionary conservation and presence of upstream AUGs (uAUGs), indicate an important regulatory role of this 5' UTR in translational control. We demonstrate that, in brain and pancreas, almost all of the native BACE1 mRNA contains the full-length 5' UTR. RNA transfection and in vitro translation show that translation is mainly inhibited by the presence of the uAUGs. We provide a mutational analysis that highlight the second uAUG as the main inhibitory element while mutations of all four uAUGs fully de-repress translation. Furthermore, we have evidence that a sequence within the region 222-323 of the BACE1 5' UTR has a stimulatory effect on translation that might depend on the presence of trans-acting factors.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. I. Nikolaev, S. Deutsch, R. Genolet, C. Borel, L. Parand, C. Ucla, F. Schutz, G. Duriaux Sail, Y. Dupre, P. Jaquier-Gubler, et al. Transcriptional and post-transcriptional profile of human chromosome 21 Genome Res., August 1, 2009; 19(8): 1471 - 1479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-X. Wang, B. W. Rajeev, A. J. Stromberg, N. Ren, G. Tang, Q. Huang, I. Rigoutsos, and P. T. Nelson The Expression of MicroRNA miR-107 Decreases Early in Alzheimer's Disease and May Accelerate Disease Progression through Regulation of {beta}-Site Amyloid Precursor Protein-Cleaving Enzyme 1 J. Neurosci., January 30, 2008; 28(5): 1213 - 1223. [Abstract] [Full Text] [PDF]
|
|