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Internal translation initiation mediated by the angiogenic factor Tie2
Eun-Hee Park1, Joseph M Lee, Jaime D Blais
1Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada.
The Journal of Biological Chemistry
|April 2, 2005
Summary
This study reveals how Tie2 mRNA translation persists during hypoxia. A cap-independent mechanism involving the Tie2 5' untranslated region (UTR) ensures blood vessel maturation protein production under stress.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Tie2 (Tunica interna endothelial cell kinase 2) is crucial for blood vessel maturation.
- Maintaining Tie2 production is vital, especially under hypoxic conditions.
- The mechanisms governing Tie2 mRNA translation under stress are not fully understood.
Purpose of the Study:
- To elucidate the mechanism ensuring Tie2 mRNA translation during hypoxia.
- To analyze the structure and function of the Tie2 5'-untranslated region (UTR).
Main Methods:
- Transcription start site mapping to identify mRNA isoforms.
- Structure/function analysis of the Tie2 5'-UTR.
- Investigating internal ribosome binding and cap-independent translation initiation.
Main Results:
- Identified multiple Tie2 mRNA isoforms with long 5'-UTRs (>350 nucleotides).
- Discovered five upstream open reading frames within the 5'-UTR.
- Demonstrated cap-independent translation initiation via internal ribosome binding.
Conclusions:
- The Tie2 5'-UTR possesses regulatory elements enabling translation initiation.
- A cap-independent mechanism secures Tie2 mRNA translation under hypoxic conditions.
- This provides a framework for understanding Tie2 production stability.