title: Evolutionary patterns of metazoan microRNAs reveal targeting principles in the let-7 and miR-10 families.
abstract: MicroRNAs (miRNAs) regulate gene output by targeting degenerate elements in mRNAs and have undergone drastic expansions in higher metazoan genomes. The evolutionary advantage of maintaining copies of highly similar miRNAs is not well understood, nor is it clear what unique functions, if any, miRNA family members possess. Here, we study evolutionary patterns of metazoan miRNAs, focusing on the targeting preferences of the let-7 and miR-10 families. These studies reveal hotspots for sequence evolution with implications for targeting and secondary structure. High-throughput screening for functional targets reveals that each miRNA represses sites with distinct features and regulates a large number of genes with cooperative function in regulatory networks. Unexpectedly, given the high degree of similarity, single-nucleotide changes grant miRNA family members with distinct targeting preferences. Together, our data suggest complex functional relationships among miRNA duplications, novel expression patterns, sequence change, and the acquisition of new targets.
authors.affiliation: Molecular and Cellular Biology Graduate Program, Arizona State University, Tempe, Arizona 85287, USA.|Virginia G. Piper Center For Personalized Diagnostics, The Biodesign Institute at Arizona State University, Tempe, Arizona 85287, USA.|School of Life Sciences, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Justin M
authors.identifier: 0000-0002-3021-3993
authors.initials: JM
authors.lastname: Wolter
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Hoai Huang Thi
authors.initials: HH
authors.lastname: Le
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Linse
authors.affiliation: Virginia G. Piper Center For Personalized Diagnostics, The Biodesign Institute at Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Godlove
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona 85287, USA.|Barrett Honors College, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Thuy-Duyen
authors.initials: TD
authors.lastname: Nguyen
authors.affiliation: Molecular and Cellular Biology Graduate Program, Arizona State University, Tempe, Arizona 85287, USA.|Virginia G. Piper Center For Personalized Diagnostics, The Biodesign Institute at Arizona State University, Tempe, Arizona 85287, USA.|School of Life Sciences, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Kasuen
authors.initials: K
authors.lastname: Kotagama
authors.affiliation: Molecular and Cellular Biology Graduate Program, Arizona State University, Tempe, Arizona 85287, USA.|School of Life Sciences, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Alissa
authors.initials: A
authors.lastname: Lynch
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Rawls
authors.affiliation: Virginia G. Piper Center For Personalized Diagnostics, The Biodesign Institute at Arizona State University, Tempe, Arizona 85287, USA.|School of Life Sciences, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Marco
authors.identifier: 0000-0001-7551-8793
authors.initials: M
authors.lastname: Mangone
mesh_terms: D000818:Animals; D017124:Conserved Sequence / Q000235:genetics; D004330:Drosophila / Q000235:genetics; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics; D009348:Nematoda / Q000235:genetics; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics
chemical_list: C569259:MIRN10 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; C487931:mirnlet7 microRNA, human