Differential utilization of upstream AUGs in the beta-secretase mRNA suggests that a shunting mechanism regulates translation.

ABSTRACT: beta-Secretase [also known as the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1)] is an enzyme involved in the production of A beta-amyloid plaques in the brains of patients with Alzheimer's disease. The enhanced production of this enzyme occurs without corresponding changes in BACE1 mRNA levels. The complex 5' leader of BACE1 mRNA contains three upstream ORFs (uORFs) preceding the BACE1 initiation codon. In this study, we investigated how this 5' leader affects translation efficiency as a first step in understanding the enhanced production of the enzyme in the disease. Using reporter constructs in transfected mammalian cell lines and cell-free lysates, we showed that the translation mediated by the BACE1 5' leader is cap-dependent and inhibited by cis-acting segments contai

SUBMITTER: Rogers GW 

PROVIDER: S-EPMC365699 | biostudies-literature | 2004 Mar

REPOSITORIES: biostudies-literature