Chemical shift prediction of RNA imino groups: application toward characterizing RNA excited states

Yanjiao Wang,Tairan Yuwen,Xiuying Jiang,Ge Han,Yi Xue

doi:10.1038/s41467-021-21840-x

Yanjiao Wang, Tairan Yuwen + Show 3 more

Open Access

https://doi.org/10.1038/s41467-021-21840-x

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Abstract

NH groups in proteins or nucleic acids are the most challenging target for chemical shift prediction. Here we show that the RNA base pair triplet motif dictates imino chemical shifts in its central base pair. A lookup table is established that links each type of base pair triplet to experimental chemical shifts of the central base pair, and can be used to predict imino chemical shifts of RNAs to remarkable accuracy. Strikingly, the semiempirical method can well interpret the variations of chemical shifts for different base pair triplets, and is even applicable to non-canonical motifs. This finding opens an avenue for predicting chemical shifts of more complicated RNA motifs. Furthermore, we combine the imino chemical shift prediction with NMR relaxation dispersion experiments targeting both 15N and 1HN of the imino group, and verify a previously characterized excited state of P5abc subdomain including an earlier speculated non-native G•G mismatch.

Highlights

NH groups in proteins or nucleic acids are the most challenging target for chemical shift prediction
Imino chemical shift prediction of RNAs based on base pair triplets
It has been reported that the chemical shift of a nonexchangeable proton in RNA A-form helical regions can be predicted within an accuracy of root-mean-square deviation

Summary

Introduction

NH groups in proteins or nucleic acids are the most challenging target for chemical shift prediction. The semiempirical method can well interpret the variations of chemical shifts for different base pair triplets, and is even applicable to non-canonical motifs. This finding opens an avenue for predicting chemical shifts of more complicated RNA motifs. The established lookup table can be used to accurately predict imino chemical shifts of RNA residues located in the center of base pair triplets. Using UUCG tetraloop as the structural model, we confirm the great potential of this method in predicting chemical shifts of noncanonical motifs We demonstrate this chemical shift prediction approach can be of great help in the secondary structure determination of RNA excited states (ESs), when combined with 15N and 1HN NMR relaxation dispersion (RD) experiments

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