Abstract
BackgroundSequence determines the three-dimensional structure of RNAs, and thereby plays an important role in carrying out various biological functions. RNA duplexes containing Watson-Crick (WC) basepairs, interspersed with non-Watson-Crick basepairs, are the dominant structural unit and form the scaffold for the 3-dimensional structure of RNA. It is therefore crucial to understand the geometric variation in the dinucleotide steps that form the helices. We have carried out a detailed analysis of the dinucleotide steps formed by AU and GC Watson-Crick basepairs in RNA structures (both free and protein bound) and compared the results to that seen in DNA. Further, the effect of protein binding on these steps was examined by comparing steps in free RNA structures with protein bound RNA structures.ResultsCharacteristic sequence dependent geometries are observed for the RR, RY and YR type of dinucleotide steps in RNA. Their geometric parameters show correlated variations that are different from those observed in B-DNA helices. Subtle, but statistically significant differences are seen in roll, slide and average propeller-twist values, between the dinucleotide steps of free RNA and protein bound RNA structures. Many non-canonical cross-strand and intra-strand hydrogen bonds were identified that can stabilise the RNA dinucleotide steps, among which YR steps show presence of many new unreported interactions.ConclusionsOur work provides for the first time a detailed analysis of the conformational preferences exhibited by Watson-Crick basepair containing steps in RNA double helices. Overall, the WC dinucleotide steps show considerable conformational variability. Furthermore, we have identified hydrogen bond interactions in several of the dinucleotide steps that could play a role in determining the preferred geometry, in addition to the intra-basepair hydrogen bonds and stacking interactions. Protein binding affects the conformation of the steps that are in direct contact, as well as allosterically affect the steps that are not in direct physical contact.
Highlights
Sequence determines the three-dimensional structure of RNAs, and thereby plays an important role in carrying out various biological functions
We focus only on the dinucleotide steps formed by the two canonical WC basepairs (AU and GC) of the cisWW family, which constitute a major proportion of the helical steps and compare them to the corresponding A-like and Blike DNA steps
In our crystal dataset we focused only on the dinucleotide steps formed by WC basepair that belong to the cisWW family (~74%), to compare with equivalent dinucleotide steps in DNA helices
Summary
Sequence determines the three-dimensional structure of RNAs, and thereby plays an important role in carrying out various biological functions. We have carried out a detailed analysis of the dinucleotide steps formed by AU and GC Watson-Crick basepairs in RNA structures (both free and protein bound) and compared the results to that seen in DNA. The helical regions in DNA are comprised almost exclusively of canonical Watson-Crick (AT and GC) basepairs, which form 10 unique dinucleotide steps. An RNA duplex consists of canonical WC basepairs (AU and GC), that are paired along Watson-Crick edge in cis orientation (cisWW family), as well as basepairs involving the Hoogsteen and Sugar edges. We focus only on the dinucleotide steps formed by the two canonical WC basepairs (AU and GC) of the cisWW family, which constitute a major proportion of the helical steps and compare them to the corresponding A-like and Blike DNA steps
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