Phase Separation in Germ Cells and Development

Dodson, Anne E.; Kennedy, Scott

doi:10.1016/j.devcel.2020.09.004

Cited by 61 publications

(69 citation statements)

References 145 publications

(238 reference statements)

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“…Nuages are membraneless electron-dense cytoplasmic condensates. It has been suggested that nuage in germ cells may form via liquid-liquid phase separation [ 63 ]. Notably, DDX4, an essential factor for piRNA biogenesis, undergoes phase separation both in vitro and in cells [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

yama, a mutant allele of Mov10l1, disrupts retrotransposon silencing and piRNA biogenesis

et al. 2021

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Piwi-interacting RNAs (piRNAs) play critical roles in protecting germline genome integrity and promoting normal spermiogenic differentiation. In mammals, there are two populations of piRNAs: pre-pachytene and pachytene. Transposon-rich pre-pachytene piRNAs are expressed in fetal and perinatal germ cells and are required for retrotransposon silencing, whereas transposon-poor pachytene piRNAs are expressed in spermatocytes and round spermatids and regulate mRNA transcript levels. MOV10L1, a germ cell-specific RNA helicase, is essential for the production of both populations of piRNAs. Although the requirement of the RNA helicase domain located in the MOV10L1 C-terminal region for piRNA biogenesis is well known, its large N-terminal region remains mysterious. Here we report a novel Mov10l1 mutation, named yama, in the Mov10l1 N-terminal region. The yama mutation results in a single amino acid substitution V229E. The yama mutation causes meiotic arrest, de-repression of transposable elements, and male sterility because of defects in pre-pachytene piRNA biogenesis. Moreover, restricting the Mov10l1 mutation effects to later stages in germ cell development by combining with a postnatal conditional deletion of a complementing wild-type allele causes absence of pachytene piRNAs, accumulation of piRNA precursors, polar conglomeration of piRNA pathway proteins in spermatocytes, and spermiogenic arrest. Mechanistically, the V229E substitution in MOV10L1 reduces its interaction with PLD6, an endonuclease that generates the 5′ ends of piRNA intermediates. Our results uncover an important role for the MOV10L1-PLD6 interaction in piRNA biogenesis throughout male germ cell development.

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Section: Discussionmentioning

confidence: 99%

yama, a mutant allele of Mov10l1, disrupts retrotransposon silencing and piRNA biogenesis

et al. 2021

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“…The switch-like decisions during germ cell development are proposed to be closely related to the formation of large protein complexes, including large granules, also known as membraneless organelles (for review [47,48]). In this regard, new ideas about the cotranslational assembly of multisubunit protein complexes with the participation of a chaperone, based on rigorous experiments, are of particular interest [2,[49][50][51].…”

Section: Discussionmentioning

confidence: 99%

Detection of the germline specific NAC protein paralog enriched by intrinsically disordered regions inDrosophila melanogaster

Kogan

Mikhaleva

et al. 2021

Preprint

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Nascent polypeptide associated complex (NAC) consisting of α- and β-subunits is an essential conserved ubiquitously expressed ribosome-associated protein in eukaryotes. NAC is considered as a chaperone and co-translational regulator of nascent protein sorting providing homeostasis of cellular proteins. Here we discovered the germinal cell specific NAC (gNAC) homologue, which differs from the ubiquitously expressed NAC by the presence of expanded intrinsically disordered regions (IDRs) at the N- and C-ends of the α- and β-subunits, respectively. We propose this evolutionary acquisition of long IDRs drive gNAC to endow both the specific conformational plasticity for binding client proteins and novel functions regulated by post-transcriptional modifications (PTM). At the same time, we demonstrated that the well-known lethal effect of the loss of ubiquitous NAC-β is suppressed by ectopic expression of its germinal paralog indicating the absence of strict functional differences between the ubiquitous and germline NAC-β subunit paralogs for protein homeostasis.

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“…Membrane‐less granules have been found to display specialized behaviors more readily observable in in vitro LLPS assemblies such as fusion, fission, wetting, shearing, dynamicity, and so forth (Banani et al, 2017; Dodson & Kennedy, 2020) (Box 1). Notably, the endoplasmic reticulum (ER) has been demonstrated to be capable of acting as an anchorage for membrane‐less organelles through specialized contact‐sites and exert limited regulatory control over assembly and fission of SGs and PBs (Lee et al, 2020).…”

Section: Rnp Granulesmentioning

confidence: 99%

Germ cell ribonucleoprotein granules in different clades of life: From insects to mammals

Mukherjee

2021

WIREs RNA

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Ribonucleoprotein (RNP) granules are no newcomers in biology. Found in all life forms, ranging across taxa, these membrane‐less “organelles” have been classified into different categories based on their composition, structure, behavior, function, and localization. Broadly, they can be listed as stress granules (SGs), processing bodies (PBs), neuronal granules (NGs), and germ cell granules (GCGs). Keeping in line with the topic of this review, RNP granules present in the germ cells have been implicated in a wide range of cellular functions including cellular specification, differentiation, proliferation, and so forth. The mechanisms used by them can be diverse and many of them remain partly obscure and active areas of research. GCGs can be of different types in different organisms and at different stages of development, with multiple types coexisting in the same cell. In this review, the different known subcategories of GCGs have been studied with respect to five distinct model organisms, namely, Drosophila, Caenorhabditis elegans, Xenopus, Zebrafish, and mammals. Of them, the cytoplasmic polar granules in Drosophila, P granules in C. elegans, balbiani body in Xenopus and Zebrafish, and chromatoid bodies in mammals have been specifically emphasized upon. A descriptive account of the same has been provided along with insights into our current understanding of their functional significance with respect to cellular events relating to different developmental and reproductive processes. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA‐Protein Complexes RNA Export and Localization > RNA Localization RNA in Disease and Development > RNA in Disease

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Phase Separation in Germ Cells and Development

Cited by 61 publications

References 145 publications

yama, a mutant allele of Mov10l1, disrupts retrotransposon silencing and piRNA biogenesis

yama, a mutant allele of Mov10l1, disrupts retrotransposon silencing and piRNA biogenesis

Detection of the germline specific NAC protein paralog enriched by intrinsically disordered regions inDrosophila melanogaster

Germ cell ribonucleoprotein granules in different clades of life: From insects to mammals

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