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Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale
10:56

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
PubMed

Insights

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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