Exploring the Role of 5’ Alternative Splicing and of the 3’-Untranslated Region of Cathepsin B mRNA
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R. Zwicky
Abstract
The cysteine peptidase cathepsin B is responsible for connective tissue breakdown in several diseases. The pathological expression of cathepsin B may depend on the structure of its mRNA. We investigated the translational efficiency of the cathepsin B mRNA untranslated regions (UTRs) using fusion constructs to green fluorescent protein (GFP) and luciferase. Transfection of fusion constructs with GFP and luciferase containing the full-length 5'-UTR, the variant lacking exon 2, and that lacking exons 2 and 3 into mammalian cells, resulted in modulation of the biosynthetic rate of cathepsin B in a cell-specific manner. Constructs missing these exons were biosynthetically more efficient than the full-length counterpart. Luciferase was cloned upstream of the 3'-UTR, downstream of the 5'- UTR, or sandwiched between the 5' and the 3'-UTR. The UTRs of cathepsin B downregulated luciferase biosynthesis moderately when present individually, with the 3'-UTR being more efficient than the 5'-UTR, and downregulated it even more when present simultaneously. A truncated cathepsin B-GFP chimeric product derived from the 5'-UTR missing exons 2 and 3 induced cell death. The increased biosynthetic rate and abnormal trafficking of cathepsin B observed in pathologies such as cancer and osteoarthritis may depend on alternative splicing of pre-mRNA.
Copyright © 2003 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- Protein Prenyltransferases: Anchor Size, Pseudogenes and Parasites
- Redox Regulation of Cell Growth and Cell Death
- Are Histones the Targets for Flavan-3-ols (Catechins) in Nuclei?
- Exploring the Role of 5’ Alternative Splicing and of the 3’-Untranslated Region of Cathepsin B mRNA
- Interaction of Maize Chromatin-Associated HMG Proteins with Mononucleosomes: Role of Core and Linker Histones
- Transcriptional Silencing of the TFPI-2 Gene by Promoter Hypermethylation in Choriocarcinoma Cells
- Solubilisation and Properties of the Sialate-4-O-Acetyltransferase from Guinea Pig Liver
- A Peroxidase from Lepista irina Cleaves β,β-Carotene to Flavor Compounds
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- Ovarian Cancer Cell Proliferation and Motility Is Induced by Engagement of Integrin αvβ3/Vitronectin Interaction
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