Novel conformation of an RNA structural switch - PubMed
- ️Sun Jan 01 2012
. 2012 Nov 20;51(46):9257-9.
doi: 10.1021/bi301372t. Epub 2012 Nov 12.
Affiliations
- PMID: 23134175
- PMCID: PMC3508625
- DOI: 10.1021/bi301372t
Free PMC article
Novel conformation of an RNA structural switch
Scott D Kennedy et al. Biochemistry. 2012.
Free PMC article
Abstract
The RNA duplex, (5'GACGAGUGUCA)(2), has two conformations in equilibrium. The nuclear magnetic resonance solution structure reveals that the major conformation of the loop, 5'GAGU/3'UGAG, is novel and contains two unusual Watson-Crick/Hoogsteen GG pairs with G residues in the syn conformation, two A residues stacked on each other in the center of the helix with inverted sugars, and two bulged-out U residues. The structure provides a benchmark for testing approaches for predicting local RNA structure and a sequence that allows the design of a unique arrangement of functional groups and/or a conformational switch into nucleic acids.
Figures
![Figure 1](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b46/3508625/872e55ebaeb6/bi-2012-01372t_0002.gif)
Imino proton spectra for RNA duplexes with the 5′GAGU/3′UGAG internal loop. Secondary structures of the major conformations are shown at the right. Peaks labeled with X are from the minor duplex conformation. The peak at 14.3 ppm in trace a is from a minor hairpin species. (a and b) Self-complementary sequences. (c and d) Non-self-complementary sequences. Black peaks and nucleotides are from the duplex half that is equivalent to the self-complementary duplex, and green peaks and nucleotides are from the duplex half that has a different sequence. (a and c) Natural nucleotides. (b and d) Duplexes with 8-Br-G6. Sample conditions: 80 mM NaCl, 0.05 mM EDTA, 20 mM sodium phosphate, pH 6, 1 °C.
![Figure 2](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b46/3508625/e593f531d7ac/bi-2012-01372t_0003.gif)
Watergate–NOESY spectrum of 5′GAC
GABr
GUGAGA/3′ACUG
UBr
GAGCUC. Residues labeled with an asterisk are in the second strand. The regions displayed include cross-peaks for A5 and A5* aromatic protons. Two large cross-peaks labeled with blue filled circles are G4 H8–G4 H1′ and G4* H8–G4* H1′ cross-peaks and indicate that G4 and G4* are in the glycosidic syn conformation. Data were acquired at −2 °C with a 200 ms mixing time, except the diagonal panel, which was acquired at 1 °C with a 400 ms mixing time.
![Figure 3](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b46/3508625/2c9efca49dde/bi-2012-01372t_0004.gif)
Major conformation of the 5′
GAGU3′/3′
UGAG5′ RNA internal loop. The secondary structure is shown at the top with residues colored as in the 3D model: (a) front view and (b) 90° rotation. (c) Potential stabilizing hydrogen bonds from A5 amino protons to 2′-oxygens of cross-strand G4* and A5*.
Similar articles
-
Spasic A, Kennedy SD, Needham L, Manoharan M, Kierzek R, Turner DH, Mathews DH. Spasic A, et al. RNA. 2018 May;24(5):656-672. doi: 10.1261/rna.064527.117. Epub 2018 Feb 6. RNA. 2018. PMID: 29434035 Free PMC article.
-
Hammond NB, Tolbert BS, Kierzek R, Turner DH, Kennedy SD. Hammond NB, et al. Biochemistry. 2010 Jul 13;49(27):5817-27. doi: 10.1021/bi100332r. Biochemistry. 2010. PMID: 20481618 Free PMC article.
-
Parallel nucleic acid helices with Hoogsteen base pairing: symmetry and structure.
Raghunathan G, Miles HT, Sasisekharan V. Raghunathan G, et al. Biopolymers. 1994 Dec;34(12):1573-81. doi: 10.1002/bip.360341202. Biopolymers. 1994. PMID: 7531510
-
Takahashi S, Sugimoto N. Takahashi S, et al. Acc Chem Res. 2021 May 4;54(9):2110-2120. doi: 10.1021/acs.accounts.0c00734. Epub 2021 Feb 16. Acc Chem Res. 2021. PMID: 33591181 Review.
-
New insights into Hoogsteen base pairs in DNA duplexes from a structure-based survey.
Zhou H, Hintze BJ, Kimsey IJ, Sathyamoorthy B, Yang S, Richardson JS, Al-Hashimi HM. Zhou H, et al. Nucleic Acids Res. 2015 Apr 20;43(7):3420-33. doi: 10.1093/nar/gkv241. Epub 2015 Mar 26. Nucleic Acids Res. 2015. PMID: 25813047 Free PMC article. Review.
Cited by
-
Surprising Sequence Effects on GU Closure of Symmetric 2 × 2 Nucleotide RNA Internal Loops.
Berger KD, Kennedy SD, Schroeder SJ, Znosko BM, Sun H, Mathews DH, Turner DH. Berger KD, et al. Biochemistry. 2018 Apr 10;57(14):2121-2131. doi: 10.1021/acs.biochem.7b01306. Epub 2018 Mar 23. Biochemistry. 2018. PMID: 29570276 Free PMC article.
-
Chen JL, Bellaousov S, Tubbs JD, Kennedy SD, Lopez MJ, Mathews DH, Turner DH. Chen JL, et al. Biochemistry. 2015 Nov 17;54(45):6769-82. doi: 10.1021/acs.biochem.5b00833. Epub 2015 Nov 3. Biochemistry. 2015. PMID: 26451676 Free PMC article.
-
DSSR-enabled innovative schematics of 3D nucleic acid structures with PyMOL.
Lu XJ. Lu XJ. Nucleic Acids Res. 2020 Jul 27;48(13):e74. doi: 10.1093/nar/gkaa426. Nucleic Acids Res. 2020. PMID: 32442277 Free PMC article.
-
Spasic A, Kennedy SD, Needham L, Manoharan M, Kierzek R, Turner DH, Mathews DH. Spasic A, et al. RNA. 2018 May;24(5):656-672. doi: 10.1261/rna.064527.117. Epub 2018 Feb 6. RNA. 2018. PMID: 29434035 Free PMC article.
-
Wales DJ, Disney MD, Yildirim I. Wales DJ, et al. J Phys Chem B. 2019 Jan 10;123(1):57-65. doi: 10.1021/acs.jpcb.8b09139. Epub 2019 Jan 2. J Phys Chem B. 2019. PMID: 30517788 Free PMC article.
References
-
- Atkins J. F., Gesteland R. F., and Cech T. R. (2011) RNA Worlds from Life’s Origins to Diversity in Gene Regulation, Cold Spring Harbor Laboratory Press, Plainview, NY.
-
- Bradley P.; Misura K. M.; Baker D. (2005) Science 309, 1868–1871. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous