title: Functional and evolutionary significance of human microRNA seed region mutations.
abstract: MicroRNAs have emerged in recent years as important regulators of cell function in both normal and diseased cells. MiRNAs coordinately regulate large suites of target genes by mRNA degradation and/or translational inhibition. The mRNA target specificities of miRNAs in animals are primarily encoded within a 7 nt "seed region" mapping to positions 2-8 at the molecule's 5' end. We here combine computational analyses with experimental studies to explore the functional significance of sequence variation within the seed region of human miRNAs. The results indicate that a substitution of even a single nucleotide within the seed region changes the spectrum of mRNA targets by >50%. The high functional cost of even single nucleotide changes within seed regions is consistent with their high sequence conservation among miRNA families both within and between species and suggests processes that may underlie the evolution of miRNA regulatory control.
authors.affiliation: Integrated Cancer Research Center, School of Biology and Parker H. Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Dr., Atlanta, Georgia 30332-0363, United States of America.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Hill
authors.affiliation: Integrated Cancer Research Center, School of Biology and Parker H. Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Dr., Atlanta, Georgia 30332-0363, United States of America.
authors.forename: Neda
authors.initials: N
authors.lastname: Jabbari
authors.affiliation: Integrated Cancer Research Center, School of Biology and Parker H. Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Dr., Atlanta, Georgia 30332-0363, United States of America.
authors.forename: Lilya V
authors.initials: LV
authors.lastname: Matyunina
authors.affiliation: Integrated Cancer Research Center, School of Biology and Parker H. Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Dr., Atlanta, Georgia 30332-0363, United States of America.
authors.forename: John F
authors.initials: JF
authors.lastname: McDonald
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment
chemical_list: D035683:MicroRNAs