The Rodent-Specific MicroRNA Cluster within the Sfmbt2 Gene is Imprinted and Essential for Placental Development [miRNA]

ABSTRACT: MicroRNAs (miRNAs) represent small noncoding RNAs that are involved in physiologic and developmental processes by negatively regulating expression of target genes. They exist as individual miRNA genes or as polycistronically transcribed gene clusters. The largest miRNA cluster in mice is located in intron 10 of the Sfmbt2 gene, and contains 72 miRNA precursor sequences within approximately 50 kb. Although this miRNA cluster emerged recently in the rodent genome, probably coincidentally with the acquisition of the imprinted control of Sfmbt2, very little is known about its functions. In this study, we generated mice lacking the entire Sfmbt2 miRNA cluster to elucidate its functions during development. Like the Sfmbt2 gene, the Sfmbt2 miRNAs were expressed in the placenta predominantly from the paternal allele. Loss of the paternal allele resulted in severely impaired development of the spongiotrophoblast layer, which usually comprises about half of the fetal placenta. This phenotype was associated with fetal developmental delay or lethality, leading to significant decreases in the number of fetuses and their weights at term. Microarray analysis identified that at least 30 miRNAs in the cluster were actively transcribed in wild-type placentas. Among the predicted targets of these miRNAs, 132 genes were upregulated in the miRNA-deleted placentas. Some of the genes most significantly upregulated, including Gkn2 and Runx1, are known to inhibit cell proliferation by inducing cell cycle arrest or apoptosis. Thus, the Sfmbt2 miRNAs play essential roles in promoting trophoblastic cell proliferation in the placenta, cooperating with the host gene under the same paternal expression control.

ORGANISM(S): Mus musculus

PROVIDER: GSE82054 | GEO | 2017/02/01

SECONDARY ACCESSION(S): PRJNA323832

REPOSITORIES: GEO