Design of Multi-Stable RNA Molecules

We show that the problem of designing RNA sequences that can fold into multiple stable secondary structures can be transformed into a combinatorial optimization problem that can be solved by means of simple heuristics. Hence it is feasible to design RNA switches with prescribed strucutral alternatives. We discuss the theoretical background and present an efficient tool that allows the design of various types of switches. We argue that both the general properties of the sequence-structure map of RNA secondary structures and the ease with which our design tool finds bi-stable RNAs, strongly indicates that RNA switches are easily accessible in evolution. Thus RNA switches are likely not exceptional instances of interesting RNA behavior but rather examples of an ubiquitous paradigm.

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