title: The characterization of microRNA-mediated gene regulation as impacted by both target site location and seed match type.
abstract: MicroRNAs (miRNAs) are small RNA molecules that play important roles in gene regulation and translational repression. The mechanisms that facilitate miRNA target binding and recognition have been extensively studied in recent years. However, it is still not well known how the miRNA regulation is affected by the location and the flanking sequences of miRNA target sites. In this study, we systematically quantify the contribution of a wide spectrum of target sites on miRNA-mediated gene expression regulation. Our study investigates target sites located in four different gene regions, including 3' untranslated regions, coding sequences, 5' untranslated regions and promoter regions. We have also introduced four additional non-canonical types of seed matches beyond the canonical seed matches, and included them in our study. Computational analysis of quantitative proteomic data has demonstrated that target sites located in different regions impact the miRNA-mediated repression differently but synergistically. In addition, we have shown the synergistic effects among non-canonical seed matches and canonical ones that enhance the miRNA regulatory effects. Further systematic analysis on the site accessibility near the target regions and the secondary structure of the mRNA sequences have demonstrated substantial variations among target sites of different locations and of different types of seed matches, suggesting the mRNA secondary structure could explain some of the difference in the miRNA regulatory effects impacted by these different target sites. Our study implies miRNAs might regulate their targets under different mechanisms when target sites vary in both their locations and the types of seed matches they contain.
authors.affiliation: Department of Neurobiology and Anatomy, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Neurobiology and Anatomy, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Zixing
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurobiology and Anatomy, University of Texas Health Science Center at Houston, Houston, Texas, United States of America; University of Texas Graduate School of Biomedical Science, Houston, Texas, United States of America.
authors.forename: Yin
authors.initials: Y
authors.lastname: Liu
mesh_terms: D001205:Ascorbic Acid; D001665:Binding Sites; D002762:Cholecalciferol; D019295:Computational Biology; D003198:Computer Simulation; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives; D005786:Gene Expression Regulation; D035683:MicroRNAs / Q000502:physiology*; D009539:Nicotinic Acids; D009690:Nucleic Acid Conformation; D010936:Plant Extracts; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA; D059629:Signal-To-Noise Ratio
chemical_list: C524255:HUM 5007; D035683:MicroRNAs; D009539:Nicotinic Acids; D010936:Plant Extracts; D002762:Cholecalciferol; D003687:Dehydroepiandrosterone; D001205:Ascorbic Acid