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• W2330702948 abstract "Noncoding Y RNAs are small stem-loop RNAs that are involved in different cellular processes, including the regulation of DNA replication. An evolutionarily conserved small domain in the upper stem of vertebrate Y RNAs has an essential function for the initiation of chromosomal DNA replication. Here we provide a structure-function analysis of this essential RNA domain under physiological conditions. Solution state nuclear magnetic resonance and far-ultraviolet circular dichroism spectroscopy show that the upper stem domain of human Y1 RNA adopts a locally destabilized A-form helical structure involving eight Watson-Crick base pairs. Within this helix, two G:C base pairs are highly stable even at elevated temperatures and therefore may serve as clamps to maintain the local structure of the helix. These two stable G:C base pairs frame three unstable base pairs, which are located centrally between them. Systematic substitution mutagenesis results in a disruption of the ordered A-form helical structure and in the loss of DNA replication initiation activity, establishing a positive correlation between folding stability and function. Our data thus provide a structural basis for the evolutionary conservation of key nucleotides in this RNA domain that are essential for the functionality of noncoding Y RNAs during the initiation of DNA replication." @default.
• W2330702948 created "2016-06-24" @default.
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• W2330702948 date "2014-09-05" @default.
• W2330702948 modified "2023-10-17" @default.
• W2330702948 title "Nucleotide Contributions to the Structural Integrity and DNA Replication Initiation Activity of Noncoding Y RNA" @default.
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• W2330702948 doi "https://doi.org/10.1021/bi500470b" @default.
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• W2330702948 hasPublicationYear "2014" @default.
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