The widespread impact of mammalian MicroRNAs on mRNA repression and evolution.
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.
Farh
Kyle Kai-How
KK
Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, and Howard Hughes Medical Institute, 9 Cambridge Center, Cambridge, MA 02142, USA.
Grimson
Andrew
A
Jan
Calvin
C
Lewis
Benjamin P
BP
Johnston
Wendy K
WK
Lim
Lee P
LP
Burge
Christopher B
CB
Bartel
David P
DP
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
D035683:MicroRNAs; D012333:RNA, Messenger; D020506:Untranslated Regions