Spb

Fig. 10.3 Structural principles of RNA and DNA supramolecular building blocks. Various examples of 2°, 3° and 4° structure motifs commonly used in DNA (a) and RNA (b) nanostructures. Small single arrows specify the geometry adopted by helical elements. (a) Contiguous helices tend to stack on the top of each other. In a DNA 3-way junction, one of the helices is generally more flexible than the other two. DNA 4-way junctions also present some degrees of flexibility [25]. For 4° assembly, DNA units can be joined through noncovalent sticky-tails connectors [159] (top right) or through internal loop-loop interactions that fold into paranemic crossover junctions (PX) that do not interpenetrate topologically [170] (bottom right); (b) RNA 2° structure elements can form flexible hinges at the level of single-stranded regions, internal loops or multi-way junctions (left). Specific set of nucleotides can also direct the formation of rigid 3° structure motifs with distinct helical geometry [32-34]. (Center panel, top to bottom): the ''right angle'' motif [35]; the internal loop E and kink turn motifs; two distinct 3-way junctions that specify for different helical geometries [38]; the 4 way-junction motif from the hairpin ribozyme [104, 176]; the class 2 tRNA 5-helix junction motif. RNA 4° interactions (Right panel) used for generating supramolecular assembling interfaces are (from top to bottom): tails connector [35], loop-loop (''kissing'') interactions [35, 180] and the double GNRA loop-receptor interaction [103].

structures of natural RNA molecules can be seen as mosaics of recurrent and modular 3° structure motifs [30]. Recently, a rich treasure-trove of structural motifs has been identified and compiled by data mining of known NMR and crystal-lographic atomic structures of RNA [32-34]. They specify a precise geometry of helical elements and can mediate stereochemically precise and readily reversible 3° and 4° interactions (Fig. 10.3b). Among them are single-strand junctions like the U turn, ''hook'' turn and the right-angle motif [35]; terminal loops like thermostable GNRA and UNCG loops, T-loops, internal loops such as loop E and loop C [36, 37]; the kink turn [37]; and different classes of 3 and 4 way junctions motifs [38]; pseudoknots, kissing-loops and loop-receptor motifs (for a complete survey of structure motifs see Refs. [32, 34]). Interestingly, RNA motifs make an extensive use of the 2 '-OH group to form specific 3° contacts and numerous longrange RNA-RNA interactions take advantage of the 2 '-OH to create compact 3-D RNA structures. Thus, by relying on different structural features, RNA and DNA motifs are structurally different at a 3° structure level. Some 3° motifs, like G-tetrads and triple helices can however form with either RNA or DNA.

Rather than relying solely on 2° structural elements, the structure of an RNA can be engineered at a three-dimensional level by encoding the structural information corresponding to rigid 3° structural motifs within its sequence. Additionally, as thermodynamically stable structural entities, larger RNA domains or full molecules such as the P4-P6 domain of group I ribozyme, the tRNA motif, natural riboswitches and RNA enzymes can themselves be used as scaffolds to engineer new artificial architectures (Sections 2.2.3 and 4). The separation of energy levels between 2° and 3° structures of RNA is distinct for stable natural RNAs, with 2° structure elements being more stable than 3° elements [39, 40]. For a complex RNA object, the dependence of the 3° structure on the presence of the extended and correct 2° structure might therefore be a necessity to avoid kinetically trapped misfolded states.

10.2.1.4 Quaternary Structure Principles

At a quaternary (4°) structure level, RNA and DNA modular units can assemble further into complex and highly modular supramolecular architectures in a predictable manner by using base-pair rules or specific, selective non-Watson-Crick interactions as organizational instructions (Fig. 10.3). The dimensionality of these nanostructures is directly related to the shape, geometry, orientation and number of assembling interfaces present at the level of their constitutive building blocks (Fig. 10.4). Brucale and colleagues proposed an interesting classification of nucleic acid nanostructures according to their topology and dimensionality [41]. Objects of dimensionality zero (0-D), which mathematically correspond to a point, are supramolecular architectures of finite size that can best be described as nonreducible modular tiles. These tiles can be modular but formed of distinct non-repetitive units. Objects of dimensionality one (1-D) are made of units with at least two interfaces leading to growth into one direction (Fig. 10.4). Dimensionality two (2-D) is based on a rectangular coordinate system commonly defined by two perpendicular axes within a plane. 2-D assemblies require at least three inter

DNA RNA

Fig. 10.4 Supramolecular dimensionalities of nucleic acid architectures. Modularity is expressed at the supramolecular level: RNA and DNA units can be engineered to assemble into nanostructures of different dimensionalities [41]. The dimensionality of supramolecular objects can be defined in term of interconnections, spatial arrangement of constitutive units and directional assembly growth.

Fig. 10.4 Supramolecular dimensionalities of nucleic acid architectures. Modularity is expressed at the supramolecular level: RNA and DNA units can be engineered to assemble into nanostructures of different dimensionalities [41]. The dimensionality of supramolecular objects can be defined in term of interconnections, spatial arrangement of constitutive units and directional assembly growth.

faces to allow the assembly to grow at least in two directions that are all circumscribed within a plane. Dimensionality three is defined by a 3-D coordinate system that provides the three physical dimensions of space: height, width, and length. 3-D objects are characterized by units with at least four nonplanar assembling interfaces that allow the assembly growth within and out of the plane in the Cartesian space. Kinetic motion is sometimes described as a fourth dimension (4-D).

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