title: The role of RNA structure at 5' untranslated region in microRNA-mediated gene regulation.
abstract: Recent studies have suggested that the secondary structure of the 5' untranslated region (5' UTR) of messenger RNA (mRNA) is important for microRNA (miRNA)-mediated gene regulation in humans. mRNAs that are targeted by miRNA tend to have a higher degree of local secondary structure in their 5' UTR; however, the general role of the 5' UTR in miRNA-mediated gene regulation remains unknown. We systematically surveyed the secondary structure of 5' UTRs in both plant and animal species and found a universal trend of increased mRNA stability near the 5' cap in mRNAs that are regulated by miRNA in animals, but not in plants. Intra-genome comparison showed that gene expression level, GC content of the 5' UTR, number of miRNA target sites, and 5' UTR length may influence mRNA structure near the 5' cap. Our results suggest that the 5' UTR secondary structure performs multiple functions in regulating post-transcriptional processes. Although the local structure immediately upstream of the start codon is involved in translation initiation, RNA structure near the 5' cap site, rather than the structure of the full-length 5' UTR sequences, plays an important role in miRNA-mediated gene regulation.
authors.affiliation: Research Center for Learning Sciences, Southeast University, Nanjing, Jiangsu 210096, China Wanjun.Gu@gmail.com akdongyi01@cau.ac.kr tongzhou@email.arizona.edu.
authors.forename: Wanjun
authors.initials: W
authors.lastname: Gu
authors.affiliation: School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, Jiangsu 210096, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Research Center for Learning Sciences, Southeast University, Nanjing, Jiangsu 210096, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Medicine, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Physiology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Ko
authors.affiliation: Department of Medicine, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D017360:Arabidopsis / Q000235:genetics; D001482:Base Composition; D001665:Binding Sites / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000235:genetics; D012315:RNA Caps / Q000737:chemistry; D020871:RNA Stability / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D035683:MicroRNAs; D012315:RNA Caps; D012313:RNA
keywords: 5′ untranslated region; RNA structure; gene regulation; microRNA