Reciprocal expression of lin-41 and the microRNAs let-7 and mir-125 during mouse embryogenesis.
In C. elegans, heterochronic genes control the timing of cell fate determination during development. Two heterochronic genes, let-7 and lin-4, encode microRNAs (miRNAs) that down-regulate a third heterochronic gene lin-41 by binding to complementary sites in its 3'UTR. let-7 and lin-4 are conserved in mammals. Here we report the cloning and sequencing of mammalian lin-41 orthologs. We find that mouse and human lin-41 genes contain predicted conserved complementary sites for let-7 and the lin-4 ortholog, mir-125, in their 3'UTRs. Mouse lin-41 (Mlin-41) is temporally expressed in developing mouse embryos, most dramatically in the limb buds. Mlin-41 is down-regulated during mid-embryogenesis at the time when mouse let-7c and mir-125 RNA levels are up-regulated. Our results suggest that mammalian lin-41 is temporally regulated by miRNAs in order to direct key developmental events such as limb formation.
Schulman
Betsy R Maller
BR
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Esquela-Kerscher
Aurora
A
Slack
Frank J
FJ
D000595:Amino Acid Sequence; D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015152:Blotting, Northern; D003001:Cloning, Molecular; D017124:Conserved Sequence / Q000235:genetics; D017931:DNA Primers; D004622:Embryo, Mammalian / Q000378:metabolism*; D005121:Extremities / Q000196:embryology; D040461:Gene Components; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; C511366:LIN-41 protein, mouse; D035683:MicroRNAs; D014157:Transcription Factors