LST-1 is a bifunctional regulator that feeds back on Notch-dependent transcription to regulate C. elegans germline stem cells

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(39)

Опубликована: Сен. 20, 2023

Notch signaling regulates stem cells across animal phylogeny. C. elegans activates transcription of two genes, lst-1 and sygl-1, that encode potent regulators germline cells. The LST-1 protein in distinct ways: It promotes self-renewal posttranscriptionally also restricts by a poorly understood mechanism. Its promoting activity resides its N-terminal region, while restricting C-terminal region requires the Zn finger. Here, we report limits down-regulating Notch-dependent transcription. We detect nucleus, addition to previously known cytoplasmic localization. lowers nascent transcript levels at both sygl-1 loci but not let-858, Notch-independent locus. key components activation complex, LAG-1 DNA binding intracellular domain (NICD). Genetically, an finger mutant increases strength gain- loss-of-function GLP-1/Notch receptor mutants. Biochemically, co-immunoprecipitates with from nematode extracts, suggesting direct effect. is thus bifunctional regulator coordinates posttranscriptional transcriptional mechanisms single protein. This bifunctionality relies on bipartite architecture bolstered generation isoforms, one specialized for downregulation. A conserved theme worms human coupling PUF-mediated RNA repression together feedback same

Язык: Английский

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A Transcription Factor Functional Atlas of Germline Development

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Янв. 26, 2024

Fertility requires the faithful proliferation of germ cells and their differentiation into gametes. Controlling these cellular states demands precise timing expression gene networks. Transcription factors (TFs) play critical roles in networks that influence cell development. There has, however, been no functional analysis entire TF repertoire controlling vivo Here, we analyzed germline architecture to systematically investigate function 364 germline-expressed TFs Caenorhabditis elegans line. Using germline-specific knockdown, automated counting, high-content nuclei plasma membrane organization, identify 156 with discrete autonomous functions. By identifying control cycle, proliferation, differentiation, structure fertility, have created an atlas for mechanistic dissection behavior gamete production.

Язык: Английский

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A nucleic acid binding protein map of germline regulation in Caenorhabditis elegans

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 11, 2024

Fertility requires the faithful proliferation of germ cells and their differentiation into gametes. Controlling these cellular states demands precise timing expression gene networks. Nucleic acid binding proteins (NBPs) play critical roles in networks that influence cell development. There has, however, been no functional analysis entire NBP repertoire controlling vivo Here, we analyzed germline architecture to systematically investigate function 364 germline-expressed NBPs Caenorhabditis elegans line. Using germline-specific knockdown, automated counting, high-content nuclei plasma membrane organization, identify 156 with discrete autonomous functions. By identifying control cycle, proliferation, differentiation, structure fertility, have created an atlas for mechanistic dissection behavior gamete production.

Язык: Английский

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The PUF RNA-binding protein, FBF-2, maintains stem cells without binding to RNA

Опубликована: Окт. 25, 2024

Abstract Like all canonical PUF proteins, C. elegans FBF-2 binds to specific RNAs via tripartite recognition motifs (TRMs). Here we report that an mutant protein cannot bind RNA, is nonetheless biologically active and maintains stem cells. This unexpected result challenges the conventional wisdom RBPs must achieve biological activity. Also unexpectedly, interactions with partner proteins can compensate for loss of RNA-binding. only loses activity when its RNA-binding are both defective. These findings highlight complementary contributions protein.

Язык: Английский

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Dynamics of Notch-dependent transcriptional bursting in its native context

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2018, Номер unknown

Опубликована: Дек. 15, 2018

Transcription is well known to be inherently stochastic and episodic, but the regulation of transcriptional dynamics not understood. Here we analyze how Notch signaling modulates bursting during animal development. Our focus transcription in germline stem cells nematode C. elegans. Using MS2 system visualize nascent transcripts live imaging record dynamics, as a function position within intact animal. We find that Notch-dependent activation indeed bursty; wild-type burst duration (ON-time) rather than pauses between bursts (OFF-time) or mean intensity; mutant receptor, which compromised for assembly into factor complex, primarily modifies size (duration x intensity). To our knowledge, this work first metazoan by canonical pathway its native context.

Язык: Английский

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Faculty Opinions recommendation of The Germline-Specific Factor OEF-1 Facilitates Coordinated Progression Through Germ Cell Development in Caenorhabditis elegans.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Год журнала: 2018, Номер unknown

Опубликована: Июнь 18, 2018

The purpose of germ cells is to ensure the faithful transmission genetic material next generation.To develop into mature gametes, must pass through cell cycle checkpoints while maintaining totipotency and genomic integrity.How coordinate developmental events simultaneously protecting their unique fate not well understood.Here, we characterize a novel nuclear protein, Oocyte-Excluded Factor-1 (OEF-1), with highly specific germline expression in Caenorhabditis elegans.OEF-1 initially detected early embryogenesis expressed nuclei all during larval stages.In adults, OEF-1 abruptly decreases just prior oocyte differentiation.In oef-1 mutants, progression accelerated, resulting subtle defects at multiple stages development.Lastly, primarily associated bodies germlineexpressed genes, as such excluded from X chromosome.We hypothesize that may regulate rate development, providing insight how these critical maturation are coordinated.

Язык: Английский

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Faculty Opinions recommendation of An RNA-Binding Multimer Specifies Nematode Sperm Fate.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Год журнала: 2018, Номер unknown

Опубликована: Ноя. 22, 2018

FOG-3 is a master regulator of sperm fate in Caenorhabditis elegans and homologous to Tob/BTG proteins, which mammals are monomeric adaptors that recruit enzymes RNA binding proteins.Here, we determine the crystal structure vitro demonstrate forms dimers can multi-merize.The multimeric has basic surface potential, suggestive nucleic acid.Consistent with prediction, binds directly nearly 1,000 RNAs nematode spermatogenic germ cells.Most 3 ′ UTR, most targets (94%) oogenic mRNAs, even though assayed cells.When tethered reporter mRNA, represses its expression.Together these findings elucidate molecular mechanism specification reveal evolution protein from form acquisition distinct mode mRNA repression.

Язык: Английский

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