Structural dynamics control the MicroRNA maturation pathway.

• Type of Material: Article
• Authors: Paul Dallaire, Université de Montréal; Huiping Tan, Emory University; Keith Szulwach, Emory University; Christopher Ma, Emory University; Peng Jin, Emory University; François Major, Université de Montréal
• Language: English
• Date: 2016-11-16
• Publisher: Oxford University Press (OUP)
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. For commercial re-use, please contact [e-mail].
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/nar/gkw793
• Title of Journal or Parent Work: Nucleic Acids Research
• ISSN: 0305-1048
• Volume: 44
• Issue: 20
• Start Page: 9956
• End Page: 9964
• Grant/Funding Information: Funding for open access charge: NSERC.; Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN/04539-2014 to F.M.]; Canadian Institutes of Health Research (CIHR) [MOP-93679 to F.M.]; National Institutes of Health [R01GM088813 to F.M.]; Human Frontier Science Program [RGP0002/2009-C to F.M.].
• Research Categories: Biology, Genetics; Health Sciences, Oncology

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.