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Mutual regulation of spermatogenesis-speciﬁc Argonaute proteins and Insulin/IGF-1 signaling in aging control [RNA-Seq]

ABSTRACT: The potential role of small interfering RNAs (siRNAs) produced from double-stranded RNA in aging has not been fully addressed. The networks of genes regulated by siRNAs and their partner Argonaute proteins are best understood in C. elegans, a pioneering model of aging and small RNA studies. Here, we describe synergistic lifespan extension of insulin/IGF-1 signaling (IIS) mutant age- 1(hx546) by rde-4 or alg-3; alg-4 deﬁciencies. By analyzing gene expression and siRNA populations in these IIS and RNAi mutants, we show here that redundant spermatogenesis-speciﬁc Argonautes ALG-3 and ALG-4 are capable of regulating IIS, potentially through direct control of the Major Sperm Protein (MSP) genes in the germline. MSPs and MSP domains of some mammalian proteins are secreted and directly inhibit the Eph receptor (EphR). In turn, EphR interacts with and destabilizes PTEN, a major negative regulator of IIS. We show that enhanced MSP expression correlates with EphR mislocalization and elevated PTEN levels in oocytes of alg-3/4(-) worms. At the same time, ALG-3/4 expression is regulated by IIS. Thus, we propose mutual regulation of IIS and ALG-3/4 through secreted ligands.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE293149 | GEO | 2026/02/19

REPOSITORIES: GEO

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Mutual regulation of spermatogenesis-speciﬁc Argonaute proteins and Insulin/IGF-1 signaling in aging control [smallRNA-Seq]

Project description:The potential role of small interfering RNAs (siRNAs) produced from double-stranded RNA in aging has not been fully addressed. The networks of genes regulated by siRNAs and their partner Argonaute proteins are best understood in C. elegans, a pioneering model of aging and small RNA studies. Here, we describe synergistic lifespan extension of insulin/IGF-1 signaling (IIS) mutant age-1(hx546) by rde-4 or alg-3; alg-4 deﬁciencies. By analyzing gene expression and siRNA populations in these IIS and RNAi mutants, we show here that redundant spermatogenesis-speciﬁc Argonautes ALG-3 and ALG-4 are capable of regulating IIS, potentially through direct control of the Major Sperm Protein (MSP) genes in the germline. MSPs and MSP domains of some mammalian proteins are secreted and directly inhibit the Eph receptor (EphR). In turn, EphR interacts with and destabilizes PTEN, a major negative regulator of IIS. We show that enhanced MSP expression correlates with EphR mislocalization and elevated PTEN levels in oocytes of alg-3/4(-) worms. At the same time, ALG-3/4 expression is regulated by IIS. Thus, we propose mutual regulation of IIS and ALG-3/4 through secreted ligands.

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The Vasa homolog RDE-12 engages target mRNA and a secondary-Argonaute WAGO-1 to promote RNAi in C. elegans

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The Vasa homolog RDE-12 engages target mRNA and a secondary-Argonaute WAGO-1 to promote RNAi in C. elegans

2014-06-24 | E-GEOD-54396 | biostudies-arrayexpress

Small RNA-mediated genetic switches coordinate ALG-3/4 small RNA pathway function

Project description:Coordination of gene regulatory networks is necessary for proper execution of cellular programs throughout development. RNA interference (RNAi) is an essential regulatory mechanism in all metazoans. Proper RNAi-mediated gene regulation requires coordination of several RNAi branches to ensure homeostasis. For example, in C. elegans, the Argonautes, ALG-3 and ALG-4, are expressed specifically during spermatogenesis (L4 stage) and bind small interfering RNAs (siRNAs) complementary to sperm-enriched genes. We find that alg-3 and alg-4 are regulated by siRNAs. Our work shows that gene switches are operated via these siRNAs to regulate the Argonautes’ expression in a temporal manner. This RNAi-to-RNAi regulatory cascade is essential for coordinating ALG-3/4 pathway function, particularly during heat stress, to provide thermotolerant sperm-based fertility. This work provides insight into one regulatory motif used to maintain RNAi homeostasis, across developmental stages, despite environmental stressors. As RNAi pathways are evolutionarily conserved, other species likely use similar regulatory architectures to maintain RNAi homeostasis.

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