One of the great challenges for emerging fields in nanobiotechnology and synthetic biology is to be able to control the three-dimensional structures of biomolecular components with a high degree of precision. The simplest way to accomplish this is by studying and understanding the way that nature has already solved these problems for biomolecular assembly. Stable RNAs are modular three-dimensional architectures that take advantage of recurrent structural motifs to form extensive networks of non-covalent tertiary interactions. A limited set of basic structural components can account for the formation of most structural motifs uncovered in ribosomal and stable RNAs. The sequence networks resulting from the structural relationships shared by these RNA motifs can be used as a protolanguage for assisting the prediction and rational design of RNA tertiary structures. Experimental methods for comparing and characterizing structural RNA motifs that define helical stacking, bending and branching or/and long-range assembly are presented. In vitro selection is used to generate new classes of RNA loop/receptor interaction. Using RNA protolanguage, new varieties of multi-helix RNA junctions that fold in a single stacking conformer are designed. The synthesis of well-defined polyhedral RNA nanoparticles defined by tertiary structure with full control over composition stoichiometry and spatial addressability is demonstrated. This work establishes that RNA tertiary structure can be used as a full-edged protolanguage to program RNA sequences to fold into any arbitrary shapes with self-assembling and ligand-responsive behavior, and lays part of the foundation for a general method of RNA design and construction.
|Commitee:||Hayes, Christopher, Perona, John, Waite, Herbert|
|School:||University of California, Santa Barbara|
|School Location:||United States -- California|
|Source:||DAI-B 71/05, Dissertation Abstracts International|
|Subjects:||Molecular biology, Biochemistry, Nanotechnology|
|Keywords:||Molecular evolution, Nanostructures, RNA, Self-assembly, Synthetic biology, Tertiary folds|
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