Alternative Ways to Think About Cellular Internal Ribosome Entry
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Internal ribosome entry sites (IRESs) are specialized mRNA elements that allow recruitment of eukaryotic ribosomes to naturally uncapped mRNAs or to capped mRNAs under conditions in which cap-dependent translation is inhibited. Putative cellular IRESs have been proposed to play crucial roles in stress responses, development, apoptosis, cell cycle control, and neuronal function. However, most of the evidence for cellular IRES activity rests on bicistronic reporter assays, the reliability of which has been questioned. Here, the mechanisms underlying cap-independent translation of cellular mRNAs and the contributions of such translation to cellular protein synthesis are discussed. I suggest that the division of cellular mRNAs into mutually exclusive categories of “cap-dependent” and “IRES-dependent” should be reconsidered and that the implications of cellular IRES activity need to be incorporated into our models of cap-dependent initiation.
DepartmentMassachusetts Institute of Technology. Department of Biology
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology (ASBMB)
Gilbert, W. V. “Alternative Ways to Think About Cellular Internal Ribosome Entry.” Journal of Biological Chemistry 285.38 (2010): 29033–29038.
Author's final manuscript