A dynamic RNA loop in an IRES affects multiple steps of elongation factor-mediated translation initiation
Abstract
Internal ribosome entry sites (IRESs) are powerful model systems to understand how the translation machinery can be manipulated by structured RNAs and for exploring inherent features of ribosome function. The intergenic region (IGR) IRESs from the Dicistroviridae family of viruses are structured RNAs that bind directly to the ribosome and initiate translation by co-opting the translation elongation cycle. These IRESs require an RNA pseudoknot that mimics a codon-anticodon interaction and contains a conformationally dynamic loop. We explored the role of this loop and found that both the length and sequence are essential for translation in different types of IGR IRESs and from diverse viruses. We found that loop 3 affects two discrete elongation factor-dependent steps in the IRES initiation mechanism. Our results show how the IRES directs multiple steps after 80S ribosome placement and highlights the often underappreciated significance of discrete conformationally dynamic elements within the context of structured RNAs.
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Reviewing Editor
- Rachel Green, Johns Hopkins School of Medicine, United States
Version history
- Received: April 16, 2015
- Accepted: November 1, 2015
- Accepted Manuscript published: November 2, 2015 (version 1)
- Version of Record published: December 23, 2015 (version 2)
Copyright
© 2015, Ruehle et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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