RNA Secondary Structures Regulate Adsorption of Fragments onto Flat Substrates.

Simón Poblete,Anže Božič,Matej Kanduč,Rudolf Podgornik,Horacio V Guzman

doi:10.1021/acsomega.1c04774

Abstract

RNA is a functionally rich molecule with multilevel, hierarchical structures whose role in the adsorption to molecular substrates is only beginning to be elucidated. Here, we introduce a multiscale simulation approach that combines a tractable coarse-grained RNA structural model with an interaction potential of a structureless flat adsorbing substrate. Within this approach, we study the specific role of stem-hairpin and multibranch RNA secondary structure motifs on its adsorption phenomenology. Our findings identify a dual regime of adsorption for short RNA fragments with and without the secondary structure and underline the adsorption efficiency in both cases as a function of the surface interaction strength. The observed behavior results from an interplay between the number of contacts formed at the surface and the conformational entropy of the RNA molecule. The adsorption phenomenology of RNA seems to persist also for much longer RNAs as qualitatively observed by comparing the trends of our simulations with a theoretical approach based on an ideal semiflexible polymer chain.

Highlights

One particular question we address is the role of different soft ribonucleic acid (RNA) secondary structure motifs in the adsorption phenomenology and the
All three RNA fragments were extracted from previous experimental studies on the genome of satellite tobacco mosaic virus (STMV), whose secondary structure has been determined by the SHAPE chemical probing method.[43,44]
Our coarse-grained model generates a 3D representation of the three RNA fragments and supports secondary structure restraints based on the primary sequence and interactions connection between the inherent RNA structure and the deconvolved from an X-ray structure database

Summary

■ INTRODUCTION

The ability of ribonucleic acid (RNA) to influence biological processes occurring inside living cells[1] has generated a lot of interest and has provided a driving force for innovative strategies in ambitious nanomedical applications.[2−6] RNA is a flexible polyelectrolyte with highly adaptable conformations and with self-associating base pairs creates a variety of complex structural motifs, which sets it apart from the commonly more rigid and structurally much less diverse DNA.[7−9] Unlike proteins, RNA acquires its structure in a hierarchical way, first assuming a secondary structure a pattern of base pairs followed by the formation of a threedimensional tertiary structure.[10−15] While RNA differs fundamentally from DNA with its pervasive, stable doublestranded form, its self-association bears some similarity with protein folding, the structural motifs present in RNA tend to be, in general, much softer and less globular.[16]. All three RNA fragments were extracted from previous experimental studies on the genome of STMV, whose secondary structure has been determined by the SHAPE chemical probing method.[43,44] It is important to remark that the three fragments of this work represent archetypal structures of the entire STMV genome, as previously obtained by chemical probing methods.[42] Our coarse-grained model generates a 3D representation of the three RNA fragments and supports secondary structure restraints based on the primary sequence and interactions connection between the inherent RNA structure and the deconvolved from an X-ray structure database We aim to invesstructure), base-paired regions are preferentially adsorbed at tigate the general role of the RNA secondary structure in lower surface interaction strengths when compared to the adsorption processes For this purpose, we model the substrate unstructured RNA.

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ METHODS

■ ACKNOWLEDGMENTS

■ REFERENCES