title: Structural dynamics control the MicroRNA maturation pathway.
abstract: MicroRNAs (miRNAs) are crucial gene expression regulators and first-order suspects in the development and progression of many diseases. Comparative analysis of cancer cell expression data highlights many deregulated miRNAs. Low expression of miR-125a was related to poor breast cancer prognosis. Interestingly, a single nucleotide polymorphism (SNP) in miR-125a was located within a minor allele expressed by breast cancer patients. The SNP is not predicted to affect the ground state structure of the primary transcript or precursor, but neither the precursor nor mature product is detected by RT-qPCR. How this SNP modulates the maturation of miR-125a is poorly understood. Here, building upon a model of RNA dynamics derived from nuclear magnetic resonance studies, we developed a quantitative model enabling the visualization and comparison of networks of transient structures. We observed a high correlation between the distances between networks of variants with that of their respective wild types and their relative degrees of maturation to the latter, suggesting an important role of transient structures in miRNA homeostasis. We classified the human miRNAs according to pairwise distances between their networks of transient structures.
authors.affiliation: Institute for Research in Immunology and Cancer, and Department of Computer Science and Operations Research, Université de Montréal, PO Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Dallaire
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Huiping
authors.initials: H
authors.lastname: Tan
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Szulwach
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.affiliation: Institute for Research in Immunology and Cancer, and Department of Computer Science and Operations Research, Université de Montréal, PO Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada Francois.Major@UMontreal.CA.
authors.forename: François
authors.initials: F
authors.lastname: Major
mesh_terms: D020029:Base Pairing; D002460:Cell Line; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D035683:MicroRNAs / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D020641:Polymorphism, Single Nucleotide; D012323:RNA Processing, Post-Transcriptional; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic
chemical_list: D035683:MicroRNAs