Work

The first crystal structures of RNA–PNA duplexes and a PNA-PNA duplex containing mismatches—toward anti-sense therapy against TREDs

Year: 2015

Type: article

Abstract: PNA is a promising molecule for antisense therapy of trinucleotide repeat disorders. We present the first crystal structures of RNA-PNA duplexes. They contain CUG repeats, relevant to myotonic dystrophy type I, and CAG repeats associated with poly-glutamine diseases. We also report the first PNA-PNA duplex containing mismatches. A comparison of the PNA homoduplex and the PNA-RNA heteroduplexes reveals PNA's intrinsic structural properties, shedding light on its reported sequence selectivity or intolerance of mismatches when it interacts with nucleic acids. PNA has a much lower helical twist than RNA and the resulting duplex has an intermediate conformation. PNA retains its overall conformation while locally there is much disorder, especially peptide bond flipping. In addition to the Watson-Crick pairing, the structures contain interesting interactions between the RNA's phosphate groups and the Π electrons of the peptide bonds in PNA.

Source: Nucleic Acids Research

DOI: 10.1093/nar/gkv1513

Authors: Agnieszka Kiliszek, Katarzyna Banaszak, Zbigniew Dauter, Wojciech Rypniewski

Institutions: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Argonne National Laboratory, National Cancer Institute

Language: English

Topic: DNA and Nucleic Acid Chemistry

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,992

Funder: European Commission