Abstract
BackgroundThe objective of this work was to investigate the hypothesis that eukaryotic Internal Ribosome Entry Sites (IRES) lack secondary structure and to examine the generality of the hypothesis.Methodology/Principal FindingsIRESs of the yeast and the fruit fly are located in the 5′UTR immediately upstream of the initiation codon. The minimum folding energy (MFE) of 60 nt RNA segments immediately upstream of the initiation codons was calculated as a proxy of secondary structure stability. MFE of the reverse complements of these 60 nt segments was also calculated. The relationship between MFE and empirically determined IRES activity was investigated to test the hypothesis that strong IRES activity is associated with weak secondary structure. We show that IRES activity in the yeast and the fruit fly correlates strongly with the structural stability, with highest IRES activity found in RNA segments that exhibit the weakest secondary structure.ConclusionsWe found that a subset of eukaryotic IRESs exhibits very low secondary structure in the 5′-UTR sequences immediately upstream of the initiation codon. The consistency in results between the yeast and the fruit fly suggests a possible shared mechanism of cap-independent translation initiation that relies on an unstructured RNA segment.
Highlights
Translation initiation by Internal Ribosome Entry Site (IRES) RNA elements is an alternative mode of translation that is utilized by some viruses and a small subset of eukaryotic mRNAs
We found that a subset of eukaryotic Internal Ribosome Entry Sites (IRES) exhibits very low secondary structure in the 59-UTR sequences immediately upstream of the initiation codon
The consistency in results between the yeast and the fruit fly suggests a possible shared mechanism of cap-independent translation initiation that relies on an unstructured RNA segment
Summary
Translation initiation by Internal Ribosome Entry Site (IRES) RNA elements is an alternative mode of translation that is utilized by some viruses and a small subset of eukaryotic mRNAs. The lack of observable sequence similarity has resulted in a widely held view that IRESs likely possess stable secondary structure allowing them to interact with the components of the translation machinery. While this is true for viral IRESs, this notion has never been critically evaluated for cellular IRESs. some of the published literature suggests that the lack of secondary structure may be important for cellular IRES activity [8,9,10,11,12]. The objective of this work was to investigate the hypothesis that eukaryotic Internal Ribosome Entry Sites (IRES) lack secondary structure and to examine the generality of the hypothesis
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