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PDBsum entry 1hg9
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DNA-RNA hybrid PDB id
1hg9

 

 

 

 

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Contents
DNA/RNA
PDB id:
1hg9
Name: DNA-RNA hybrid
Title: Solution structure of dna:rna hybrid
Structure: 5- d( Cp Tp Gp Ap Tp Ap Tp Gp C) -3. Chain: a. Engineered: yes. 5- r( Gp Cp Ap Up Ap Up Cp Ap G) -3. Chain: b. Engineered: yes
Source: Synthetic: yes. Synthetic construct. Organism_taxid: 32630. Organism_taxid: 32630
NMR struc: 40 models
Authors: M.Petersen,K.Bondensgaard,J.Wengel,J.P.Jacobsen
Key ref: K.Bondensgaard et al. (2000). Structural studies of LNA:RNA duplexes by NMR: conformations and implications for RNase H activity. Chemistry, 6, 2687-2695. PubMed id: 10985717
Date:
13-Dec-00     Release date:   02-Jan-02    
 Headers
 References

DNA/RNA chains
  C-T-G-A-T-A-T-G-C 9 bases
  G-C-A-U-A-U-C-A-G 9 bases

 

 
Chemistry 6:2687-2695 (2000)
PubMed id: 10985717  
 
 
Structural studies of LNA:RNA duplexes by NMR: conformations and implications for RNase H activity.
K.Bondensgaard, M.Petersen, S.K.Singh, V.K.Rajwanshi, R.Kumar, J.Wengel, J.P.Jacobsen.
 
  ABSTRACT  
 
We have used NMR and CD spectroscopy to study the conformations of modified oligonucleotides (locked nucleic acid, LNA) containing a conformationally restricted nucleotide (T(L)) with a 2'-O,4'-C-methylene bridge. We have investigated two LNA:RNA duplexes, d(CTGAT(L)ATGC):r(GCAUAUCAG) and d(CT(L)GAT(L)AT(L)GC):r(GCAUAUCAG), along with the unmodified DNA:RNA reference duplex. Increases in the melting temperatures of +9.6 degrees C and +8.1 degrees C per modification relative to the unmodified duplex were observed for these two LNA:RNA sequences. The three duplexes all adopt right-handed helix conformations and form normal Watson-Crick base pairs with all the bases in the anti conformation. Sugar conformations were determined from measurements of scalar coupling constants in the sugar rings and distance information derived from 1H-1H NOE measurements; all the sugars in the RNA strands of the three duplexes adopt an N-type conformation (A-type structure), whereas the sugars in the DNA strands change from an equilibrium between S- and N-type conformations in the unmodified duplex towards more of the N-type conformation when modified nucleotides are introduced. The presence of three modified T(L) nucleotides induces drastic conformational shifts of the remaining unmodified nucleotides of the DNA strand, changing all the sugar conformations except those of the terminal sugars to the N type. The CD spectra of the three duplexes confirm the structural changes described above. On the basis of the results reported herein, we suggest that the observed conformational changes can be used to tune LNA:RNA duplexes into substrates for RNase H: Partly modified LNA:RNA duplexes may adopt a duplex structure between the standard A and B types, thereby making the RNA strand amenable to RNase H-mediated degradation.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20719742 D.Ittig, A.B.Gerber, and C.J.Leumann (2011).
Position-dependent effects on stability in tricyclo-DNA modified oligonucleotide duplexes.
  Nucleic Acids Res, 39, 373-380.  
21177095 K.Wang, Z.Sun, M.Feng, A.Liu, S.Yang, Y.Chen, and X.Lin (2011).
Design of a sandwich-mode amperometric biosensor for detection of PML/RARĪ± fusion gene using locked nucleic acids on gold electrode.
  Biosens Bioelectron, 26, 2870-2876.  
20413581 G.F.Deleavey, J.K.Watts, T.Alain, F.Robert, A.Kalota, V.Aishwarya, J.Pelletier, A.M.Gewirtz, N.Sonenberg, and M.J.Damha (2010).
Synergistic effects between analogs of DNA and RNA improve the potency of siRNA-mediated gene silencing.
  Nucleic Acids Res, 38, 4547-4557.  
20151386 M.Alvira, and R.Eritja (2010).
Triplex-stabilizing properties of parallel clamps carrying LNA derivatives at the Hoogsteen strand.
  Chem Biodivers, 7, 376-382.  
20043313 S.Shukla, C.S.Sumaria, and P.I.Pradeepkumar (2010).
Exploring chemical modifications for siRNA therapeutics: a structural and functional outlook.
  ChemMedChem, 5, 328-349.  
18295505 J.Stenvang, A.N.Silahtaroglu, M.Lindow, J.Elmen, and S.Kauppinen (2008).
The utility of LNA in microRNA-based cancer diagnostics and therapeutics.
  Semin Cancer Biol, 18, 89.  
18203740 V.Pande, and L.Nilsson (2008).
Insights into structure, dynamics and hydration of locked nucleic acid (LNA) strand-based duplexes from molecular dynamics simulations.
  Nucleic Acids Res, 36, 1508-1516.  
17571058 G.Obernosterer, J.Martinez, and M.Alenius (2007).
Locked nucleic acid-based in situ detection of microRNAs in mouse tissue sections.
  Nat Protoc, 2, 1508-1514.  
17768146 I.Lebars, T.Richard, C.Di Primo, and J.J.Toulmé (2007).
NMR structure of a kissing complex formed between the TAR RNA element of HIV-1 and a LNA-modified aptamer.
  Nucleic Acids Res, 35, 6103-6114.
PDB codes: 2oom 2pn9
17908692 S.Donini, M.Clerici, J.Wengel, B.Vester, and A.Peracchi (2007).
The advantages of being locked. Assessing the cleavage of short and long RNAs by locked nucleic acid-containing 8-17 deoxyribozymes.
  J Biol Chem, 282, 35510-35518.  
16306041 C.Dash, J.P.Marino, and S.F.Le Grice (2006).
Examining Ty3 polypurine tract structure and function by nucleoside analog interference.
  J Biol Chem, 281, 2773-2783.  
16885281 K.Kubota, A.Ohashi, H.Imachi, and H.Harada (2006).
Improved in situ hybridization efficiency with locked-nucleic-acid-incorporated DNA probes.
  Appl Environ Microbiol, 72, 5311-5317.  
15653644 J.Elmén, H.Thonberg, K.Ljungberg, M.Frieden, M.Westergaard, Y.Xu, B.Wahren, Z.Liang, H.Ørum, T.Koch, and C.Wahlestedt (2005).
Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality.
  Nucleic Acids Res, 33, 439-447.  
15598818 A.Válóczi, C.Hornyik, N.Varga, J.Burgyán, S.Kauppinen, and Z.Havelda (2004).
Sensitive and specific detection of microRNAs by northern blot analysis using LNA-modified oligonucleotide probes.
  Nucleic Acids Res, 32, e175.  
15181175 F.Darfeuille, J.B.Hansen, H.Orum, C.Di Primo, and J.J.Toulmé (2004).
LNA/DNA chimeric oligomers mimic RNA aptamers targeted to the TAR RNA element of HIV-1.
  Nucleic Acids Res, 32, 3101-3107.  
15514112 J.B.Opalinska, A.Kalota, L.K.Gifford, P.Lu, K.Y.Jen, P.I.Pradeepkumar, J.Barman, T.K.Kim, C.R.Swider, J.Chattopadhyaya, and A.M.Gewirtz (2004).
Oxetane modified, conformationally constrained, antisense oligodeoxyribonucleotides function efficiently as gene silencing molecules.
  Nucleic Acids Res, 32, 5791-5799.  
12573856 M.Petersen, and J.Wengel (2003).
LNA: a versatile tool for therapeutics and genomics.
  Trends Biotechnol, 21, 74-81.  
11182314 D.A.Braasch, and D.R.Corey (2001).
Locked nucleic acid (LNA): fine-tuning the recognition of DNA and RNA.
  Chem Biol, 8, 1-7.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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