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Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale
Published on: May 17, 2014
IRES-mediated pathways to polysomes: nuclear versus cytoplasmic routes
Bert L Semler1, Marian L Waterman
1Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697, USA. blsemler@uci.edu
Trends in Microbiology
|December 18, 2007
Summary
Internal ribosome entry sites (IRES) initiate translation independently of the mRNA cap. Their function and interaction with IRES trans-acting factors (ITAFs) depend on the mRNA
Area of Science:
- Molecular Biology
- Virology
- Genetics
Background:
- Eukaryotic mRNA translation initiation occurs via cap-dependent scanning, ribosome shunting, or cap-independent internal ribosome entry.
- Internal ribosome entry sites (IRES) facilitate cap-independent translation initiation by directly binding ribosomes to internal mRNA sequences.
- IRES elements are found in viruses and cellular mRNAs, interacting with specific RNA-binding proteins called IRES trans-acting factors (ITAFs).
Purpose of the Study:
- To compare IRES elements from different sources: cytoplasmic RNA viruses, cellular mRNAs, and DNA viruses.
- To investigate the relationship between IRES function, ITAF composition, and mRNA synthesis location.
- To understand how the mRNA's pathway to polysomes influences IRES-mediated translation.
Main Methods:
- Comparative analysis of IRES sequences and structures from various viral and cellular origins.
- In silico and experimental identification of ITAFs associated with different IRES elements.
- Correlation of IRES activity with mRNA synthesis site (cytoplasmic vs. nuclear) and processing pathway.
Main Results:
- Distinct differences observed in IRES elements from RNA viruses, DNA viruses, and cellular mRNAs.
- Specific ITAF profiles are associated with IRES elements depending on their origin and cellular localization.
- IRES function is modulated by ITAF composition, reflecting the mRNA's site of synthesis and its journey to the ribosome.
Conclusions:
- ITAF composition and IRES function are key determinants of internal ribosome entry.
- The site of mRNA synthesis (cytoplasmic vs. nuclear) significantly influences IRES element characteristics and activity.
- Understanding IRES-ITAF interactions provides insights into the regulation of translation for diverse mRNA types.
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