Biomedical subjects

Luc Jaeger

Publications and source records attributed to Luc Jaeger.

9 recordsLinked to original sources

PubMed2006

The architectonics of programmable RNA and DNA nanostructures.

The past several years have witnessed the emergence of a new world of nucleic-acid-based architectures with highly predictable and programmable self-assembly properties. For almost two decades, DNA has been the primary material for nucleic acid nanoconstruction. More recently, the dramatic increase in RNA structural information led to the development of RNA architectonics, the scientific study of the principles of RNA architecture with the aim of constructing RNA nanostructures of any arbitrary size and shape. The remarkable modularity and the distinct but complementary nature of RNA and DNA nanomaterials are revealed by the various self-assembly strategies that aim to achieve control of the arrangement of matter at a nanoscale level.

Base Sequence↗

PubMed2006

Controlling RNA self-assembly to form filaments.

Fundamental control over supra-molecular self-assembly for organization of matter on the nano-scale is a major objective of nanoscience and nanotechnology. 'RNA tectonics' is the design of modular RNA units, called tectoRNAs, that can be programmed to self-assemble into novel nano- and meso-scopic architectures of desired size and shape. We report the three-dimensional design of tectoRNAs incorporating modular 4-way junction (4WJ) motifs, hairpin loops and their cognate loop-receptors to create extended, programmable interaction interfaces. Specific and directional RNA-RNA interactions at these interfaces enable conformational, topological and orientational control of tectoRNA self-assembly. The interacting motifs are precisely positioned within the helical arms of the 4WJ to program assembly from only one helical stacking conformation of the 4WJ. TectoRNAs programmed to assemble with orientational compensation produce micrometer-scale RNA filaments through supra-molecular equilibrium polymerization. As visualized by transmission electron microscopy, these RNA filaments resemble actin filaments from the protein world. This work emphasizes the potential of RNA as a scaffold for designing and engineering new controllable biomaterials mimicking modern cytoskeletal proteins.

Actin Cytoskeleton↗

PubMed2006

Construction and characterization of a gold nanoparticle wire assembled using Mg2+-dependent RNA-RNA interactions.

Magnesium-ion-mediated RNA-RNA loop-receptor interactions, in conjunction with gold nanoparticles derivatized with DNA, have been used to make self-assembled nanowires. A wire located between lithographically fabricated nanoelectrodes is demonstrated that exhibits activated conduction by electron hopping at temperatures in the 150-300 K range. These techniques have the ability to link particles between devices and in the future may be used to assemble practical circuits.

Base Sequence↗

PubMed2005

Controlled spacing of cationic gold nanoparticles by nanocrown RNA.

Using atomic force microscopy, we describe the linear arrangement of cationic gold nanoparticles directed by programmable self-assembling RNA ladders and demonstrate that the regular spacing of nanoparticles is controlled by the RNA architecture acting as nanocrown scaffoldings. Thus, precise positioning of molecular components can be accomplished with RNA not only through electrostatic but also via size and shape recognitions.

Cations↗

PubMed2005

RNA helical packing in solution: NMR structure of a 30 kDa GAAA tetraloop-receptor complex.

Tertiary interactions are critical for proper RNA folding and ribozyme catalysis. RNA tertiary structure is often condensed through long-range helical packing interactions mediated by loop-receptor motifs. RNA structures displaying helical packing by loop-receptor interactions have been solved by X-ray crystallography, but not by NMR. Here, we report the NMR structure of a 30 kDa GAAA tetraloop-receptor RNA complex. In order to stabilize the complex, we used a modular design in which the RNA was engineered to form a homodimer, with each subunit containing a GAAA tetraloop phased one helical turn apart from its cognate 11-nucleotide receptor domain. The structure determination utilized specific isotopic labeling patterns (2H, 13C and 15N) and refinement against residual dipolar couplings. We observe a unique and highly unusual chemical shift pattern for an adenosine platform interaction that reveals a spectroscopic fingerprint for this motif. The structure of the GAAA tetraloop-receptor interaction is well defined solely from experimental NMR data, shows minor deviations from previously solved crystal structures, and verifies the previously inferred hydrogen bonding patterns within this motif. This work demonstrates the feasibility of using engineered homodimers as modular systems for the determination of RNA tertiary interactions by NMR.

Base Sequence↗

PubMed2004

Building programmable jigsaw puzzles with RNA.

One challenge in supramolecular chemistry is the design of versatile, self-assembling building blocks to attain total control of arrangement of matter at a molecular level. We have achieved reliable prediction and design of the three-dimensional structure of artificial RNA building blocks to generate molecular jigsaw puzzle units called tectosquares. They can be programmed with control over their geometry, topology, directionality, and addressability to algorithmically self-assemble into a variety of complex nanoscopic fabrics with predefined periodic and aperiodic patterns and finite dimensions. This work emphasizes the modular and hierarchical characteristics of RNA by showing that small RNA structural motifs can code the precise topology of large molecular architectures. It demonstrates that fully addressable materials based on RNA can be synthesized and provides insights into self-assembly processes involving large populations of RNA molecules.

Algorithms↗

PubMed2004

Generation of a catalytic module on a self-folding RNA.

It is theoretically possible to obtain a catalytic site of an artificial ribozyme from a random sequence consisting of a limited numbers of nucleotides. However, this strategy has been inadequately explored. Here, we report an in vitro selection technique that exploits modular construction of a structurally constrained RNA to acquire a catalytic site for RNA ligation from a short random sequence. To practice the selection, a sequence of 30 nucleotides was located close to the putative reaction site in a derivative of a naturally occurring self-folding RNA whose crystal structure is known. RNAs whose activity depended on the starting three-dimensional structure were selected with 3'-5' ligation specificity, indicating that the strategy can be used to acquire a variety of catalytic sites and other functional RNA modules.

Animals↗

PubMed2004

Characterization of tectoRNA assembly with cationic conjugated polymers.

Association between RNAs with preprogrammed molecular recognition units can be quantified by using cationic, water-soluble conjugated polymers. The method uses a fluorophore-labeled probe RNA (RNA-F*), which is treated with a target structure (RNA-T). Heterodimer formation, (RNA-T/RNA-F*), increases the total negative charge on the F*-bearing macromolecule and reduces the number of negatively charged molecules (relative to unbound RNA-T+ RNA-F*). On the basis of electrostatic interactions, we anticipated more effective binding between CCP and (RNAT/RNA-F*), a reduction of the average CCP- - -F* distance, and more effective FRET upon excitation of the conjugated polymer. The resulting signals benefit from the optical amplification characteristic of emissive conjugated polymers. Solution dissociation constants can be determined by monitoring F* intensity changes as a function of [RNA-F*] and the ratio: [I(T) - I(NB)]/I(NB), where I(T) and I(NB) are the F* intensities in the presence of the target RNA (RNA-T) and a nonbinding RNA (RNA-NB), respectively, while keeping the concentration of the conjugated polymer constant. By focusing on [I(T) - I(NB)]/I(NB) as a function of RNA concentration, one can detect the concentration range wherein increased fluorescence is the result of dimerization.

Base Sequence↗

PubMed2004

A ligase ribozyme obtained from a structured pool.

Here we report the in vitro selection experiment employed to construct a catalytic site on a self-folding RNA. To practice the selection, the sequence of 30 nucleotides was located in close proximity of the putative reaction site in a derivative of a naturally occurring RNA with a well known 3D structure. The acquired catalytic RNA retained the starting 3D structure and was successfully reconstructed according to its modular structure.

Animals↗