Correlating SHAPE Signatures with Three-dimensional RNA Structures

Overview

Journal RNA

Specialty Molecular Biology

Date 2011 Jul 15

PMID 21752927

Citations 29

Authors

Eckart Bindewald

Michaela Wendeler

Michal Legiewicz

Marion K Bona

Yi Wang

Mark J Pritt

Stuart F J Le Grice

Bruce A Shapiro

Affiliations

Soon will be listed here.

Abstract

Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) is a facile technique for quantitative analysis of RNA secondary structure. In general, low SHAPE signal values indicate Watson-Crick base-pairing, and high values indicate positions that are single-stranded within the RNA structure. However, the relationship of SHAPE signals to structural properties such as non-Watson-Crick base-pairing or stacking has thus far not been thoroughly investigated. Here, we present results of SHAPE experiments performed on several RNAs with published three-dimensional structures. This strategy allows us to analyze the results in terms of correlations between chemical reactivities and structural properties of the respective nucleotide, such as different types of base-pairing, stacking, and phosphate-backbone interactions. We find that the RNA SHAPE signal is strongly correlated with cis-Watson-Crick/Watson-Crick base-pairing and is to a remarkable degree not dependent on other structural properties with the exception of stacking. We subsequently generated probabilistic models that estimate the likelihood that a residue with a given SHAPE score participates in base-pairing. We show that several models that take SHAPE scores of adjacent residues into account perform better in predicting base-pairing compared with individual SHAPE scores. This underscores the context sensitivity of SHAPE and provides a framework for an improved interpretation of the response of RNA to chemical modification.

Citing Articles

Consistent features observed in structural probing data of eukaryotic RNAs.

Yamamura K, Asai K, Iwakiri J NAR Genom Bioinform. 2025; 7(1):lqaf001.

PMID: 39885881 PMC: 11780854. DOI: 10.1093/nargab/lqaf001.

RNA:RNA interaction in ternary complexes resolved by chemical probing.

Banijamali E, Baronti L, Becker W, Sajkowska-Kozielewicz J, Huang T, Palka C RNA. 2023; 29(3):317-329.

PMID: 36617673 PMC: 9945442. DOI: 10.1261/rna.079190.122.

Advances and opportunities in RNA structure experimental determination and computational modeling.

Zhang J, Fei Y, Sun L, Zhang Q Nat Methods. 2022; 19(10):1193-1207.

PMID: 36203019 DOI: 10.1038/s41592-022-01623-y.

Characteristic chemical probing patterns of loop motifs improve prediction accuracy of RNA secondary structures.

Cao J, Xue Y Nucleic Acids Res. 2021; 49(8):4294-4307.

PMID: 33849076 PMC: 8096282. DOI: 10.1093/nar/gkab250.

Computationally reconstructing cotranscriptional RNA folding from experimental data reveals rearrangement of non-native folding intermediates.

Yu A, Gasper P, Cheng L, Lai L, Kaur S, Gopalan V Mol Cell. 2021; 81(4):870-883.e10.

PMID: 33453165 PMC: 8061711. DOI: 10.1016/j.molcel.2020.12.017.

References

Laederach A, Das R, Vicens Q, Pearlman S, Brenowitz M, Herschlag D . Semiautomated and rapid quantification of nucleic acid footprinting and structure mapping experiments. Nat Protoc. 2008; 3(9):1395-401. PMC: 2652576. DOI: 10.1038/nprot.2008.134. View

Tullius T, Dombroski B . Iron(II) EDTA used to measure the helical twist along any DNA molecule. Science. 1985; 230(4726):679-81. DOI: 10.1126/science.2996145. View

Wilkinson K, Merino E, Weeks K . Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE): quantitative RNA structure analysis at single nucleotide resolution. Nat Protoc. 2007; 1(3):1610-6. DOI: 10.1038/nprot.2006.249. View

Mortimer S, Weeks K . A fast-acting reagent for accurate analysis of RNA secondary and tertiary structure by SHAPE chemistry. J Am Chem Soc. 2007; 129(14):4144-5. DOI: 10.1021/ja0704028. View

Das R, Laederach A, Pearlman S, Herschlag D, Altman R . SAFA: semi-automated footprinting analysis software for high-throughput quantification of nucleic acid footprinting experiments. RNA. 2005; 11(3):344-54. PMC: 1262685. DOI: 10.1261/rna.7214405. View

Geissmann T, Marzi S, Romby P . The role of mRNA structure in translational control in bacteria. RNA Biol. 2009; 6(2):153-60. DOI: 10.4161/rna.6.2.8047. View

Low J, Weeks K . SHAPE-directed RNA secondary structure prediction. Methods. 2010; 52(2):150-8. PMC: 2941709. DOI: 10.1016/j.ymeth.2010.06.007. View

Wakeman C, Winkler W . Structural probing techniques on natural aptamers. Methods Mol Biol. 2009; 535:115-33. DOI: 10.1007/978-1-59745-557-2_8. View

Wilkinson K, Gorelick R, Vasa S, Guex N, Rein A, Mathews D . High-throughput SHAPE analysis reveals structures in HIV-1 genomic RNA strongly conserved across distinct biological states. PLoS Biol. 2008; 6(4):e96. PMC: 2689691. DOI: 10.1371/journal.pbio.0060096. View

10.

Deigan K, Li T, Mathews D, Weeks K . Accurate SHAPE-directed RNA structure determination. Proc Natl Acad Sci U S A. 2008; 106(1):97-102. PMC: 2629221. DOI: 10.1073/pnas.0806929106. View

11.

Regulski E, Breaker R . In-line probing analysis of riboswitches. Methods Mol Biol. 2008; 419:53-67. DOI: 10.1007/978-1-59745-033-1_4. View

12.

Watts J, Dang K, Gorelick R, Leonard C, Bess Jr J, Swanstrom R . Architecture and secondary structure of an entire HIV-1 RNA genome. Nature. 2009; 460(7256):711-6. PMC: 2724670. DOI: 10.1038/nature08237. View

13.

Serganov A, Patel D . Ribozymes, riboswitches and beyond: regulation of gene expression without proteins. Nat Rev Genet. 2007; 8(10):776-90. PMC: 4689321. DOI: 10.1038/nrg2172. View

14.

Turner K, Yi-Brunozzi H, Brinson R, Marino J, Fabris D, Le Grice S . SHAMS: combining chemical modification of RNA with mass spectrometry to examine polypurine tract-containing RNA/DNA hybrids. RNA. 2009; 15(8):1605-13. PMC: 2714758. DOI: 10.1261/rna.1615409. View

15.

Tullius T, Greenbaum J . Mapping nucleic acid structure by hydroxyl radical cleavage. Curr Opin Chem Biol. 2005; 9(2):127-34. DOI: 10.1016/j.cbpa.2005.02.009. View

16.

Scott W, Martick M, Chi Y . Structure and function of regulatory RNA elements: ribozymes that regulate gene expression. Biochim Biophys Acta. 2009; 1789(9-10):634-41. DOI: 10.1016/j.bbagrm.2009.09.006. View

17.

Zirbel C, Sponer J, Sponer J, Stombaugh J, Leontis N . Classification and energetics of the base-phosphate interactions in RNA. Nucleic Acids Res. 2009; 37(15):4898-918. PMC: 2731888. DOI: 10.1093/nar/gkp468. View

18.

Zhang L, Doudna J . Structural insights into group II intron catalysis and branch-site selection. Science. 2002; 295(5562):2084-8. DOI: 10.1126/science.1069268. View

19.

Waugh A, Gendron P, Altman R, Brown J, Case D, Gautheret D . RNAML: a standard syntax for exchanging RNA information. RNA. 2002; 8(6):707-17. PMC: 1370290. DOI: 10.1017/s1355838202028017. View

20.

Nowotny M, Yang W . Structural and functional modules in RNA interference. Curr Opin Struct Biol. 2009; 19(3):286-93. PMC: 2721689. DOI: 10.1016/j.sbi.2009.04.006. View