1QC8

NMR STRUCTURE OF TAU EXON 10 SPLICING REGULATORY ELEMENT RNA

Summary for 1QC8

• Entry DOI: 10.2210/pdb1qc8/pdb
• Descriptor: TAU EXON 10 SPLICING REGULATORY ELEMENT RNA (1 entity in total)
• Functional Keywords: alternative mrna splicing, frontotemporal dementia ftdp-17, intronic mutations, stem-loop rna structure, tau gene exon 10, rna
• Total number of polymer chains: 1
• Total formula weight: 7990.78

Authors

Varani, L.,Spillantini, M.G.,Klug, A.,Goedert, M.,Varani, G. (deposition date: 1999-05-18, release date: 1999-08-31, Last modification date: 2022-03-02)

Primary citation

Varani, L.,Hasegawa, M.,Spillantini, M.G.,Smith, M.J.,Murrell, J.R.,Ghetti, B.,Klug, A.,Goedert, M.,Varani, G.
Structure of tau exon 10 splicing regulatory element RNA and destabilization by mutations of frontotemporal dementia and parkinsonism linked to chromosome 17.
Proc.Natl.Acad.Sci.USA, 96:8229-8234, 1999

PubMed Abstract: Coding region and intronic mutations in the tau gene cause frontotemporal dementia and parkinsonism linked to chromosome 17. Intronic mutations and some missense mutations increase splicing in of exon 10, leading to an increased ratio of four-repeat to three-repeat tau isoforms. Secondary structure predictions have led to the proposal that intronic mutations and one missense mutation destabilize a putative RNA stem-loop structure located close to the splice-donor site of the intron after exon 10. We have determined the three-dimensional structure of this tau exon 10 splicing regulatory element RNA by NMR spectroscopy. We show that it forms a stable, folded stem-loop structure whose thermodynamic stability is reduced by frontotemporal dementia and parkinsonism linked to chromosome 17 mutations and increased by compensatory mutations. By exon trapping, the reduction in thermodynamic stability is correlated with increased splicing in of exon 10.

PubMed: 10393977
DOI: 10.1073/pnas.96.14.8229

Experimental method

SOLUTION NMR