Dataset Information

WD40 protein Wuho controls germline homeostasis via TRIM-NHL tumor suppressor Mei-p26 in Drosophila.

ABSTRACT: WD40 proteins control many cellular processes via protein interactions. Drosophila Wuho (Wh, a WD40 protein) controls fertility, although the involved mechanisms are unclear. Here, we show that Wh promotion of Mei-p26 (a human TRIM32 ortholog) function maintains ovarian germ cell homeostasis. Wh and Mei-p26 are epistatically linked, with wh and mei-p26 mutants showing nearly identical phenotypes, including germline stem cell (GSC) loss, stem-cyst formation due to incomplete cytokinesis between GSCs and daughter cells, and overproliferation of GSC progeny. Mechanistically, Wh interacts with Mei-p26 in different cellular contexts to induce cell type-specific effects. In GSCs, Wh and Mei-p26 promote BMP stemness signaling for proper GSC division and maintenance. In GSC progeny, Wh and Mei-p26 silence nanos translation, downregulate a subset of microRNAs involved in germ cell differentiation and suppress ribosomal biogenesis via dMyc to limit germ cell mitosis. We also found that the human ortholog of Wh (WDR4) interacts with TRIM32 in human cells. Our results show that Wh is a regulator of Mei-p26 in Drosophila germ cells and suggest that the WD40-TRIM interaction may also control tissue homeostasis in other stem cell systems.

SUBMITTER: Rastegari E

PROVIDER: S-EPMC7375833 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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WD40 protein Wuho controls germline homeostasis via TRIM-NHL tumor suppressor Mei-p26 in Drosophila.

Rastegari Elham E Kajal Kreeti K Tan Boon-Shing BS Huang Fu F Chen Ruey-Hwa RH Hsieh Tao-Shieh TS Hsu Hwei-Jan HJ

Development (Cambridge, England) 20200115 2

WD40 proteins control many cellular processes via protein interactions. Drosophila Wuho (Wh, a WD40 protein) controls fertility, although the involved mechanisms are unclear. Here, we show that Wh promotion of Mei-p26 (a human TRIM32 ortholog) function maintains ovarian germ cell homeostasis. Wh and Mei-p26 are epistatically linked, with wh and mei-p26 mutants showing nearly identical phenotypes, including germline stem cell (GSC) loss, stem-cyst formation due to incomplete ...[more]

PMID: 31941704

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Project description:The TRIM-NHL family of proteins shares a conserved domain architecture and play crucial roles in stem cell biology, fertility, and development. This review synthesizes new insights that have revolutionized our understanding of the molecular and biological functions of TRIM-NHL proteins. Multiple TRIM-NHLs have been shown to bind specific RNA sequences and structures. X-ray crystal structures of TRIM-NHL proteins in complex with RNA ligands reveal versatile modes of RNA recognition by the NHL domain. Functional and genetic analyses show that TRIM-NHL RNA-binding proteins negatively regulate the protein expression from the target mRNAs that they bind. This repressive activity plays a crucial role in controlling stem cell fate in the developing brain and differentiating germline. To highlight these paradigms, we focus on several of the most-extensively studied TRIM-NHL proteins, specifically Drosophila and vertebrate TRIM71, among others. Brat is essential for development and regulates key target mRNAs to control differentiation of germline and neural stem cells. TRIM71 is also required for development and promotes stem cell proliferation while antagonizing differentiation. Moreover, TRIM71 can be utilized to help reprogram fibroblasts into induced pluripotent stem cells. Recently discovered mutations in TRIM71 cause the neurodevelopmental disease congenital hydrocephalus and emphasize the importance of its RNA-binding function in brain development. Further relevance of TRIM71 to disease pathogenesis comes from evidence linking it to several types of cancer, including liver and testicular cancer. Collectively, these advances demonstrate a primary role for TRIM-NHL proteins in the post-transcriptional regulation of gene expression in crucial biological processes. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications Translation > Translation Regulation RNA Turnover and Surveillance > Regulation of RNA Stability.

Dataset Information

WD40 protein Wuho controls germline homeostasis via TRIM-NHL tumor suppressor Mei-p26 in Drosophila.

Publications

WD40 protein Wuho controls germline homeostasis via TRIM-NHL tumor suppressor Mei-p26 in <i>Drosophila</i>.

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