miR-17 family miRNAs are expressed during early mammalian development and regulate stem cell differentiation.
MicroRNAs are small non-coding RNAs that regulate protein expression by binding 3'UTRs of target mRNAs, thereby inhibiting translation. Similar to siRNAs, miRNAs are cleaved by Dicer. Mouse and ES cell Dicer mutants demonstrate that microRNAs are necessary for embryonic development and cellular differentiation. However, technical obstacles and the relative infancy of this field have resulted in few data on the functional significance of individual microRNAs. We present evidence that miR-17 family members, miR-17-5p, miR-20a, miR-93, and miR-106a, are differentially expressed in developing mouse embryos and function to control differentiation of stem cells. Specifically, miR-93 localizes to differentiating primitive endoderm and trophectoderm of the blastocyst. We also observe high miR-93 and miR-17-5p expression within the mesoderm of gastrulating embryos. Using an ES cell model system, we demonstrate that modulation of these miRNAs delays or enhances differentiation into the germ layers. Additionally, we demonstrate that these miRNAs regulate STAT3 mRNA in vitro. We suggest that STAT3, a known ES cell regulator, is one target mRNA responsible for the effects of these miRNAs on cellular differentiation.
Foshay
Kara M
KM
Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
Gallicano
G Ian
GI
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001755:Blastocyst / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology*; D005260:Female; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism; D051521:Fibroblast Growth Factor 5 / Q000235:genetics / Q000378:metabolism; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009024:Morphogenesis; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D000098908:Brachyury Protein
D020413:3' Untranslated Regions; D005326:Fetal Proteins; D051521:Fibroblast Growth Factor 5; D051557:Hepatocyte Nuclear Factor 4; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein; C496450:Fgf5 protein, mouse; C496593:Hnf4a protein, mouse; C494087:Stat3 protein, mouse