25-30 August 2019
Henry Ford Building
Europe/Berlin timezone

Unique quadruplex structure and anti-disease activity of RNA aptamer, and in-cell NMR of nucleic acids

29 Aug 2019, 16:45
25m
Lecture Hall B (Henry Ford Building)

Lecture Hall B

Henry Ford Building

Talk Biological applications Biomolecules

Speaker

Prof. Masato Katahira (Kyoto University)

Description

We previously identified an RNA aptamer against a prion protein, r(GGAGGAGGAGGA) (R12). We showed that R12 forms a unique quadruplex structure and reduces a level of the abnormal prion protein, PrPSc, in the mouse neuronal cells, implying its therapeutic potential as to prion diseases (1,2). We also utilized R12 to develop the K+-responsive ribozyme (3) and RNA aptamer against HIV-1 Tat protein (4), using its quadruplex formation in response to K+. Here, we reveal that RNA with analogous sequence to R12 can reduce the level of PrPSc much more efficiently. Structure determination rationalizes the higher anti-prion activity of this new RNA (5).

Some recent studies suggested that amyloid beta (Aβ) forms soluble oligomers, protofibrils and fibrils; the Aβ oligomers being more toxic than the fibrils. The Aβ oligomers reportedly bind to prion protein (PrP), which acts as a receptor on the cell membrane, possibly resulting in Alzheimer’s disease (AD) (6). Thus, it is thought that compounds that can disrupt the formation of the prion-Aβ oligomer complex may prevent AD. Here, we demonstrate that R12 inhibits the interaction of PrP with Aβ, which implies therapeutic potential of R12 to AD (7).

In-cell NMR is a promising method to obtain the information on the structure, dynamics and interaction of biomolecules. We succeeded in observing NMR signals of DNA/RNA in living human cells for the first time (8). The observed signals directly suggested the formation of DNA/RNA hairpin structures in living human cells. Further development of in-cell NMR studies of nucleic acids in human cells will be presented.

1) Nucleic Acids Res., 2013. 2) Nucleic Acids Res., 2014. 3) Chem. Commun., 2015.
4) Chem. Commun., 2017. 5) submitted. 6) Nature, 2009. 7) FEBS J., 2019. 8) PCCP, 2018.

Primary author

Prof. Masato Katahira (Kyoto University)

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