title: The widespread impact of mammalian MicroRNAs on mRNA repression and evolution.
abstract: Thousands of mammalian messenger RNAs are under selective pressure to maintain 7-nucleotide sites matching microRNAs (miRNAs). We found that these conserved targets are often highly expressed at developmental stages before miRNA expression and that their levels tend to fall as the miRNA that targets them begins to accumulate. Nonconserved sites, which outnumber the conserved sites 10 to 1, also mediate repression. As a consequence, genes preferentially expressed at the same time and place as a miRNA have evolved to selectively avoid sites matching the miRNA. This phenomenon of selective avoidance extends to thousands of genes and enables spatial and temporal specificities of miRNAs to be revealed by finding tissues and developmental stages in which messages with corresponding sites are expressed at lower levels.
authors.affiliation: Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, and Howard Hughes Medical Institute, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Kyle Kai-How
authors.initials: KK
authors.lastname: Farh
authors.forename: Andrew
authors.initials: A
authors.lastname: Grimson
authors.forename: Calvin
authors.initials: C
authors.lastname: Jan
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Lewis
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Johnston
authors.forename: Lee P
authors.initials: LP
authors.lastname: Lim
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Burge
authors.forename: David P
authors.initials: DP
authors.lastname: Bartel
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D017124:Conserved Sequence; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008322:Mammals / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D009928:Organ Specificity; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D020506:Untranslated Regions; D015027:Zebrafish / Q000235:genetics
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D020506:Untranslated Regions