title: Designing small multiple-target artificial RNAs.
abstract: MicroRNAs (miRNAs) are naturally occurring small RNAs that regulate the expression of several genes. MiRNAs' targeting rules are based on sequence complementarity between their mature products and targeted genes' mRNAs. Based on our present understanding of those rules, we developed an algorithm to design artificial miRNAs to target simultaneously a set of predetermined genes. To validate in silico our algorithm, we tested different sets of genes known to be targeted by a single miRNA. The algorithm finds the seed of the corresponding miRNA among the solutions, which also include the seeds of new artificial miRNA sequences potentially capable of targeting these genes as well. We also validated the functionality of some artificial miRNAs designed to target simultaneously members of the E2F family. These artificial miRNAs reproduced the effects of E2Fs inhibition in both normal human fibroblasts and prostate cancer cells where they inhibited cell proliferation and induced cellular senescence. We conclude that the current miRNA targeting rules based on the seed sequence work to design multiple-target artificial miRNAs. This approach may find applications in both research and therapeutics.
authors.affiliation: Département de Biochimie, Université de Montréal, Montréal, QC H3C 3J7 Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: De Guire
authors.forename: Maxime
authors.initials: M
authors.lastname: Caron
authors.forename: Nicolas
authors.initials: N
authors.lastname: Scott
authors.forename: Catherine
authors.initials: C
authors.lastname: Ménard
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Gaumont-Leclerc
authors.forename: Pascal
authors.initials: P
authors.lastname: Chartrand
authors.forename: François
authors.initials: F
authors.lastname: Major
authors.forename: Gerardo
authors.initials: G
authors.lastname: Ferbeyre
mesh_terms: D000465:Algorithms; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence; D050684:E2F Transcription Factors / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry* / Q000378:metabolism
chemical_list: D050684:E2F Transcription Factors; D035683:MicroRNAs
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