PIWI proteins play essential roles in germ cells and stem cell lineages. In Drosophila, Piwi is required in somatic niche cells and germline stem cells (GSCs) to support GSC self-renewal and differentiation. Whether and how other PIWI proteins are involved in GSC biology remains unknown. Here, we show that Aubergine (Aub), another PIWI protein, is intrinsically required in GSCs for their self-renewal and differentiation. Aub needs to be loaded with piRNAs to control GSC self-renewal and acts through direct mRNA regulation. We identify the Cbl proto-oncogene, a regulator of mammalian hematopoietic stem cells, as a novel GSC differentiation factor. Aub stimulates GSC self-renewal by repressing Cbl mRNA translation and does so in part through recruitment of the CCR4-NOT complex. This study reveals the role of piRNAs and PIWI proteins in controlling stem cell homeostasis via translational repression and highlights piRNAs as major post-transcriptional regulators in key developmental decisions.
A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal
The Drosophila poly(A)-binding protein II is ubiquitous throughout Drosophila development and has the same function in mRNA polyadenylation as its bovine homolog in vitro
D-cbl, a negative regulator of the Egfr pathway, is required for dorsoventral patterning in Drosophila oogenesis
Activation of a meiotic checkpoint during Drosophila oogenesis regulates the translation of Gurken through Chk2/Mnk
A discrete transcriptional silencer in the bam gene determines asymmetric division of the Drosophila germline stem cell
The Drosophila SDE3 homolog armitage is required for oskar mRNA silencing and embryonic axis specification
The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes
Smaug recruits the CCR4/POP2/NOT deadenylase complex to trigger maternal transcript localization in the early Drosophila embryo
Bruno inhibits the expression of mitotic cyclins during the prophase I meiotic arrest of Drosophila oocytes
Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells
MIWI associates with translational machinery and PIWI-interacting RNAs (piRNAs) in regulating spermatogenesis
Drosophila rasiRNA pathway mutations disrupt embryonic axis specification through activation of an ATR/Chk2 DNA damage response
Cutoff and aubergine mutations result in retrotransposon upregulation and checkpoint activation in Drosophila
zucchini and squash encode two putative nucleases required for rasiRNA production in the Drosophila germline
MILI, a PIWI-interacting RNA-binding protein, is required for germ line stem cell self-renewal and appears to positively regulate translation
Vasa promotes Drosophila germline stem cell differentiation by activating mei-P26 translation by directly interacting with a (U)-rich motif in its 3' UTR
The Fused/Smurf complex controls the fate of Drosophila germline stem cells by generating a gradient BMP response
Brat promotes stem cell differentiation via control of a bistable switch that restricts BMP signaling
Uniting germline and stem cells: the function of Piwi proteins and the piRNA pathway in diverse organisms
The Cutoff protein regulates piRNA cluster expression and piRNA production in the Drosophila germline
miRNA repression involves GW182-mediated recruitment of CCR4-NOT through conserved W-containing motifs.
Control of germline stem cell division frequency--a novel, developmentally regulated role for epidermal growth factor signaling
Sex-lethal enables germline stem cell differentiation by down-regulating Nanos protein levels during Drosophila oogenesis
The cochaperone shutdown defines a group of biogenesis factors essential for all piRNA populations in Drosophila
Protein tyrosine kinase regulation by ubiquitination: critical roles of Cbl-family ubiquitin ligases
Biology of PIWI-interacting RNAs: new insights into biogenesis and function inside and outside of germlines
Mei-p26 cooperates with Bam, Bgcn and Sxl to promote early germline development in the Drosophila ovary
Drosophila piwi mutants exhibit germline stem cell tumors that are sustained by elevated Dpp signaling
The CCR4 deadenylase acts with Nanos and Pumilio in the fine-tuning of Mei-P26 expression to promote germline stem cell self-renewal
Piwi is required in multiple cell types to control germline stem cell lineage development in the Drosophila ovary
Structural and biochemical insights to the role of the CCR4-NOT complex and DDX6 ATPase in microRNA repression
A DDX6-CNOT1 complex and W-binding pockets in CNOT9 reveal direct links between miRNA target recognition and silencing
Mitochondrial dysfunction reveals the role of mRNA poly(A) tail regulation in oculopharyngeal muscular dystrophy pathogenesis
Loss of Cbl and Cbl-b ubiquitin ligases abrogates hematopoietic stem cell quiescence and sensitizes leukemic disease to chemotherapy
Aubergine iCLIP Reveals piRNA-Dependent Decay of mRNAs Involved in Germ Cell Development in the Early Embryo
Coordinate post-transcriptional repression of Dpp-dependent transcription factors attenuates signal range during development
Twin Promotes the Maintenance and Differentiation of Germline Stem Cell Lineage through Modulation of Multiple Pathways
Piwi maintains germline stem cells and oogenesis in Drosophila through negative regulation of Polycomb group proteins
Aubergine Controls Germline Stem Cell Self-Renewal and Progeny Differentiation via Distinct Mechanisms
Drosophila small ovary gene is required for transposon silencing and heterochromatin organization, and ensures germline stem cell maintenance and differentiation
Differential expression of piRNAs in reprogrammed pluripotent stem cells from mouse embryonic fibroblasts
Testis single-cell RNA-seq reveals the dynamics of de novo gene transcription and germline mutational bias in Drosophila
PIWI genes and piRNAs are ubiquitously expressed in mollusks and show patterns of lineage-specific adaptation
piRNA silencing contributes to interspecies hybrid sterility and reproductive isolation in Drosophila melanogaster
Special vulnerability of somatic niche cells to transposable element activation in Drosophila larval ovaries.
Environmentally-Induced Transgenerational Epigenetic Inheritance: Implication of PIWI Interacting RNAs
Nuclear Ccr4-Not mediates the degradation of telomeric and transposon transcripts at chromatin in the Drosophila germline
Primate piRNA Cluster Evolution Suggests Limited Relevance of Pseudogenes in piRNA-Mediated Gene Regulation
Stellate Genes and the piRNA Pathway in Speciation and Reproductive Isolation of Drosophila melanogaster.
Uninvited guests: how transposable elements take advantage of Drosophila germline stem cells, and how stem cells fight back
piRNA-mediated gene regulation and adaptation to sex-specific transposon expression in D. melanogaster male germline.
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