Searching for 2D RNA geometries in bacterial genomes

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The central dogma of biology, that DNA makes RNA makes protein, was again shown to be outdated with the recent discovery of RNAs that have essential regulatory functions (e.g., metabolite-binding RNAs, transcription regulation) [2, 15]. These finding have stimulated a large effort to search for small, functional RNA motifs (either embedded inside larger messenger RNA molecules or as separate molecules in the cell). For example, it is known that cells make use of a variety of small non-coding RNAs (such as microRNAs) as a mechanism for gene regulation. The very existence of these small motifs in Nature suggests that the functional, artificial RNA molecules developed through (experimental) in vitro selection technology may shed some light on the scope and functional diversity of these small RNA molecules in vivo. The binding and catalytic properties of nucleic acid molecules are conferred by specific sequence and structural motifs. Indeed, recent discoveries show that metabolite-induced RNA conformational changes constitute another form of bacterial gene regulation [12, 20, 21]. Since in vitro selection is a process that simulates evolution, it is reasonable that novel nucleic acid motifs discovered through in vitro selection experiments may have also evolved in the cell, especially since such motifs often target molecules (e.g., ATP, cAMP, antibiotics, etc.) that are prevalent in Nature. The structure of RNA is hierarchical in nature. The primary (1D) structure of an RNA molecule is the oriented, linear ordering of the nucleotides A, C, G, and U. The secondary (2D) structure of the molecule is described by ∗To whom correspondence should be addressed 1In vitro selection is a process that mimics evolution in which a large pool of small, random-sequence RNA molecules is subjected to an iterative process that selects for a specific physical or chemical property; see [19] for a review.