Common occurrence of many small structural motifs in natural RNA molecules suggests that nature utilize s a vocabulary of sequence patterns to compose structural molecules with sophisticated topologies such as the ribosome and large ribozymes. By careful analysis of sequences and tertiary structures of natural RNAs, 3D RNA modules and their folding and assembly principles are presently gathered for generating the syntax of a proto-language for rational design and prediction of RNA 3D shapes. RNA architectonics refers to the creation of this proto-language and to its use to build new RNAs with self-assembly properties. Recently, RNA architectonics led to the reliable prediction and design of the tertiary structure of several artificial RNA building blocks able to form programmable filaments and 2D RNA arrays at the nano-scale level. As a proof of concept, we also demonstrated that structurally complex RNAs based on a syntax involving a repertoire of several different RNA motifs can self-assemble into complex supra-molecular 3D nano-particles. This studies show that RNA architectonics can be used as a tool to explore and compare the biophysical properties of various RNA tertiary structure motifs that would be otherwise more difficult to investigate in isolation or within their natural context. It also demonstrates that RNA is an ideal medium for sculpting addressable and responsive self-assembling architectures of any desired shapes in the 20 to 50 nm scale. Moreover, it suggests that RNA supra-molecular assembly can potentially lead to the development of highly sophisticated therapeutic nano-devices for biological and medical applications. References 1. Jaeger, L. & Chworos, A. (2006) The Architectonics of Programmable RNA and DNA Nanostructures. Current Opinion in Structural Biology, 16, 531-543. 2. Chworos, A, Severcan, I., Koyfman, A. Y., Wienkam, P., Oroudjev, E., Hansma, H. G. & Jaeger, L. (2004). Building programmable jigsaw puzzles with RNA. Science 306, 2068-2072. 3. Nasalean, L., Baudrey, S., Leontis, N.B. & Jaeger, L. (2006) Controlling RNA self-assembly to form filaments. Nucleic Acids Res. 34, 1381-1392 4. Bates, A.D., Callen B.P., Cooper J.M., Cosstick, R., Geary, C., Glidle, A., Jaeger, L., Pearson, J.L., Proupín-Pérez, M., Xu, C., & Cumming, D.R. S. (2006) Construction and characterization of a gold nanoparticle wire assembled using Mg2+-dependent RNA-RNA interactions. Nanoletters 6, 445-448.