Computational Investigation of RNA A-Bulges Related to the Microtubule-Associated Protein Tau Causing Frontotemporal Dementia and Parkinsonism.

摘要: Mutations in the human tau gene result alternative splicing of protein, which causes frontotemporal dementia and Parkinsonism. One disease mechanism is linked to stability a hairpin within microtubule-associated protein (MAPT) mRNA, contains an A-bulge. Here we employ computational methods investigate structural thermodynamic properties several A-bulge RNAs with different closing base-pairs. We find that current amber RNA force field has preference overstabilize base-triple over stacked states, even though some A-bulges are known prefer states according NMR studies. further determined if neighboring base-pairs AU, this situation can lead base slippage. However, when 3'-side UA base-pair, state stabilized by extra interaction not observed other sequences. suggest these systems could be used as benchmarks improve fields.