Aubergine and piRNAs promote germline stem cell self-renewal by repressing the proto-oncogene Cbl

The EMBO Journal
Patricia Rojas-RíosMartine Simonelig

Abstract

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.

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Citations

Jul 4, 2018·Molecular Reproduction and Development·Beibei BieJin Sun
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Sep 9, 2018·Development·Patricia Rojas-Ríos, Martine Simonelig
Mar 3, 2020·Frontiers in Cell and Developmental Biology·Taylor D HinnantElizabeth T Ables
Jul 1, 2020·Stem Cells·James M W R McElhinneyAbdulrahim A Sajini
Mar 20, 2019·Genome Biology and Evolution·Daniel GebertDavid Rosenkranz
Sep 22, 2020·Trends in Genetics : TIG·Anne Ramat, Martine Simonelig
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Datasets Mentioned

BETA
GSM327624
GSM872307
GSM548585
GSM948741

Methods Mentioned

BETA
immunoprecipitation
iCLIP
ubiquitination
transgenic
PCR

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