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Dr Fran莽ois Major, Institut de Recherche en Immunologie et en Canc茅rologie and D茅partement d'Informatique et de Recherche Op茅rationnelle, Universit茅 de Montr茅al. We changed the classical rationale underlying RNA structure prediction by incorporating the contributions of the non-Watson-Crick base pairs. To do so, we defined a new first-order object for representing nucleotide relationships in structured RNAs, which we call nucleotide cyclic motif (NCM) (1). In comparison to the classical stacks of Watson-Crick base pairs, the properties that make these particular building blocks appealing for structure determination are that: i) they embrace indistinctly both canonical and non-canonical base pairs; ii) they precisely designate how any nucleotide in the sequence relates to others; iii) two adjacent blocks are merged through a common base pair, allowing us to predict compatible chains of NCMs (2) and to assemble them in complete 3-D structures. We show here how the new approach i) reproduces accurately consensus/experimental 3-D structures from sequence data (cf. hairpins, polymorphic RNAs, multi-branched RNAs), ii) incorporates multiple-sequence and low-resolution data, and iii) improves the structural bases of RNAi mechanisms, such as precursor processing and siRNA targeting.