RNA secondary structures

Stem A stretch of double-stranded RNA Loop A loop of RNA Hairpin loop A very short loop 

Pseudoknot Interachon between one secondary structure element and another part of the same RNA molecule 

RNA is often depicted as a single-stranded molecule. However, in many RNA s, internal complementarity may result in secondary (and tertiary) structure in which one part of the RNA molecule forms a double-stranded region with another part of the same molecule. There are usually a number of mismatches in these structures. Names have been given to some of these structural features (Fig. 4-3). 

A single molecule of RNA often contains segments of sequence that are complementary to each other. These complementary sequences can base-pair and form helical regions of secondary structure. Interactions between the secondary structures give RNA a significant folded, three-dimensional structure. 

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The determination of the molecular weight of animal cell RNA, using electrophoresis on exponential polyacrylamide gels under fully denaturing conditions, has been described. Effects due to RNA secondary structure are fully suppressed if dry formamide and high temperatures are used.177... 

TABLE 11.1. Association Constants of Various Nucleic Acids with Neomycin. From top to bottom, various polynucleotides with their conformational preference (B- to A-form) are listed in 10 mM sodium cacodylate, 100 mM NaCl, 0.1 mM EDTA, pH 6.8. RNA targets that have previously been shown to bind neomycin are also listed. These targets are examples of RNA secondary structures that show high-affinity binding to aminoglycosides. Solution conditions for RNA targets vary as shown... 

Ding, Y. and Lawrence, C. E. (2003). A statistical sampling algorithm for RNA secondary structure prediction. Nucleic Acids Res. 31,7280-7301. 

Zuker, M. and Jacobson, A. B. (1998). Using rehabihty information to annotate RNA secondary structures. RNA 4, 669-679. 

Zuker M, Mathews DH, Turner DH (1999) Algorithms and thermodynamics for RNA secondary structure prediction a practical guide. In Barciszewski J, Clark BTC (eds) RNA biochemistry and biotechnology. NATO ASI series. Kluwer Academic Publishers, Dordrecht, pp 11-43... 

Functional RNA molecules, whether natural or produced in the lab through directed evolution, typically require distinctive secondary structures to fulfill their function for a nice example we refer to Schwienhorst [8]. These structures serve as a scaffold that allows the formation of, e. g., a catalytic site. Thus, sequence constraints observed in RNA molecules selected for a particular function, such as binding or catalysis, may be due to direct involvement in that function or due to stabilization of the structure. Predicted RNA secondary structures can be most helpful to identify such structural constraints and to interpret the results of a directed evolution experiment in terms of structure-function relationships. 

If you just want to produce the occasional drawing of an RNA secondary structure you may skip to Section 12.2.2. 

Inverse folding can be viewed as an optimization problem that can be treated with simple heuristics. This is what the RNAinverse program does for you. Input for the RNAinverse program consists of an RNA secondary structure (the target) in bracket notation (on the first line), optionally followed by a sequence to be used as the starting point of the optimization (otherwise a random start sequence is used). 

I.L. Hofacker. The Vienna RNA secondary structure server. Nucleic Acids Res., 31 3429-3431,2003. 

I.L. Hofacker, W. Fontana, P.F Stadler, S. Bonhoeffer, M. Tacker, and P. Schuster. Fast folding and comparison of RNA secondary structures (the Vienna RNA Package). Monath. Chem., 125 167-188, 1994. 

D. Mathews, J. Sabina, M. Zucker, and H. Turner. Expanded sequence dependence of thermodynamic parameters provides robust prediction of RNA secondary structure. J. Mol. Biol, 288 911-940, 1999. 

Reidys, C., Stadler, P.F., Schuster, P. (1996). Generic properties of combinatory maps. Neutral networks of RNA secondary structures. Bull. Math. Biol. 59,339-397. 

Ecker, D.J. (1993) Strategies for invasion of RNA secondary structures. In B.Lebleu and S.T.Crooke (eds) Antisense Research and Applications. CRC, Boca Raton, pp. 387-399. 

Tabemero, C., Zolotukhin, A.S., Valentin, A., Pavlakis, G.N. and Felber, B.K. (1996) The posttranscriptional control element of the simian retrovirus type 1 forms an extensive RNA secondary structure necessary for its function. J. Virol, 70,5998-6011. 

A number of bioinformatic programs can calculate the distance between RNA secondary structures and perform clustering analysis to identify ensembles of related structures (Liu et al., 2008 Torarinsson et al., 2007). Partitioning the alignment in a set of ensembles thus reduces the total number of phylogenetic variants to be considered and single representative from each ensemble can be subjected to crystallization trials. 

Since RNA secondary structure is relatively stable, RNA folding experiments which start with a sample that has been prepared in the absence of Mg2 1 generally need to anneal the sample in a suitable buffer at relatively high temperatures between 50 and 90 °C. 

RNA secondary structures and many tertiary structures are stable in the absence of any divalent cation, and may require only moderate concentrations of a monovalent salt such as KCI or NaCl. In this section, we give two examples of the calculation of Ar for such RNAs. 

Mathews, D. H., and Turner, D. H. (2006). Prediction of RNA secondary structure by free energy minimization. Cun. Opin. Struct. Biol. 16, 270-278. 

Macke TJ, Ecker DJ, Gutell RR, Gautheret D, Case DA, Sampath R. RNA-Motif, an RNA secondary structure definition and search algorithm. Nucleic Acids Res 2001 29 4724-4735. 

RNA secondary structure Most RNA molecules are single-stranded but an RNA molecule may contain regions which can form complementary base-pairing where the RNA strand loops back on itself (Fig. 2). If so, the RNA will have some double-stranded regions. Ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs) (see Topics G9 and G10, respectively) exhibit substantial secondary structure, as do some messenger RNAs (mRNAs). 

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