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296 RNA folding in vivo Renée Schroeder*, Rupert Grossberger, Andrea Pichler and Christina Waldsich RNA folding in vivo is influenced by the cellular environment, Although experiments with RNA molecules in vitro have the vectorial nature of transcription and translation, trans-acting already provided deep insights into the RNA folding factors and ion homeostasis. Specific RNA-binding proteins process, only a few approaches have been undertaken to promote RNA folding by stabilizing the native structure or by address folding in vivo. In this review, we will discuss the guiding folding. In contrast, RNA chaperones, which are believed differences between the experimental conditions of the to interact nonspecifically with RNA, were proposed to resolve in vitro studies and the situations that the RNA molecules misfolded RNA structures and to promote intermolecular might encounter in their natural context in vivo. RNA–RNA annealing. Small trans-acting noncoding RNAs are thought to modulate mRNA structures, thereby regulating gene How similar is RNA folding in vitro and in vivo? expression. So far, there is some evidence that in vitro and The approaches used to study RNA folding in vitro provide in vivo RNA folding pathways share basic features. However, it incomplete results because important features of the is unclear whether the rules deduced from in vitro folding intracellular environment cannot be reliably reproduced. experiments generally apply to in vivo conditions. However, studying folding in vivo might obscure specific conformational changes because of the complexity of Addresses biological reactions. A first attempt to compare the folding Institute of Micr