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  The thermodynamic patterns of eukaryotic genes suggest a mechanism for intron-exon recognition.

Nedelcheva-Veleva, M. N., Sarov, M., Yanakiev, I., Mihailovska, E., Ivanov, M. P., Panova, G. C., et al. (2013). The thermodynamic patterns of eukaryotic genes suggest a mechanism for intron-exon recognition. Nature Communications, 4: 2101.

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Nedelcheva-Veleva, Marina N, Author
Sarov, Mihail1, Author           
Yanakiev, Ivan, Author
Mihailovska, Eva, Author
Ivanov, Miroslav P, Author
Panova, Greta C, Author
Stoynov, Stoyno2, Author
Affiliations:
1Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society, ou_2340692              
2Max Planck Society, ou_persistent13              

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 Abstract: The essential cis- and trans-acting elements required for RNA splicing have been defined, however, the detailed molecular mechanisms underlying intron-exon recognition are still unclear. Here we demonstrate that the ratio between stability of mRNA/DNA and DNA/DNA duplexes near 3'-spice sites is a characteristic feature that can contribute to intron-exon differentiation. Remarkably, throughout all transcripts, the most unstable mRNA/DNA duplexes, compared with the corresponding DNA/DNA duplexes, are situated upstream of the 3'-splice sites and include the polypyrimidine tracts. This characteristic instability is less pronounced in weak alternative splice sites and disease-associated cryptic 3'-splice sites. Our results suggest that this thermodynamic pattern can prevent the re-annealing of mRNA to the DNA template behind the RNA polymerase to ensure access of the splicing machinery to the polypyrimidine tract and the branch point. In support of this mechanism, we demonstrate that RNA/DNA duplex formation at this region prevents pre-spliceosome A complex assembly.

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 Dates: 2013
 Publication Status: Issued
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 Identifiers: eDoc: 688470
Other: 5697
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Title: Nature Communications
Source Genre: Journal
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Pages: - Volume / Issue: 4 Sequence Number: 2101 Start / End Page: - Identifier: -