The Caenorhabditis elegans pumilio homolog, puf-9, is required for the 3'UTR-mediated repression of the let-7 microRNA target gene, hbl-1.
The Puf family of RNA-binding proteins directs cell fates by regulating gene expression at the level of translation and RNA stability. Here, we report that the Caenorhabditis elegans pumilio homolog, puf-9, controls the differentiation of epidermal stem cells at the larval-to-adult transition. Genetic analysis reveals that loss-of-function mutations in puf-9 enhance the lethality and heterochronic phenotypes caused by mutations in the let-7 microRNA (miRNA), while suppressing the heterochronic phenotypes of lin-41, a let-7 target and homolog of Drosophila Brat. puf-9 interacts with another known temporal regulator hbl-1, the Caenorhabditis elegans ortholog of hunchback. We present evidence demonstrating that puf-9 is required for the 3'UTR-mediated regulation of hbl-1, in both the hypodermis and the ventral nerve cord. Finally, we show that this regulation is dependent on a region of the hbl-1 3'UTR that contains putative Puf family binding sites as well as binding sites for the let-7 miRNA family, suggesting that puf-9 and let-7 may mediate hypodermal seam cell differentiation by regulating common targets.
Nolde
Mona J
MJ
Department of Molecular, Cellular and Developmental Biology, Yale University, P.O. Box 208103, New Haven, CT 06520, USA.
Saka
Nazli
N
Reinert
Kristy L
KL
Slack
Frank J
FJ
D020413:3' Untranslated Regions / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D015801:Helminth Proteins; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C520835:Puf-9 protein, C elegans; C474486:hbl-1 protein, C elegans; C474488:let-7 microRNA, C elegans; C074333:pum protein, Drosophila