Strong eukaryotic IRESs have weak secondary structure.
BACKGROUND
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.


RESULTS
IRESs 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.


CONCLUSIONS
We 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.
Xia
Xuhua
X
Department of Biology and Center for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Canada.
Holcik
Martin
M
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D018387:Codon, Initiator; D004331:Drosophila melanogaster / Q000235:genetics; D005057:Eukaryotic Cells / Q000502:physiology*; D005786:Gene Expression Regulation; D009690:Nucleic Acid Conformation; D012441:Saccharomyces cerevisiae / Q000235:genetics
D020121:5' Untranslated Regions; D018387:Codon, Initiator