LIP-1 phosphatase controls the extent of germline proliferation in Caenorhabditis elegans

Lee, Myon‐Hee; Hook, Brad; Lamont, Liana B.; Wickens, Marvin; Kimble, Judith

doi:10.1038/sj.emboj.7600901

Cited by 70 publications

(122 citation statements)

References 37 publications

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“…Anti-GLD-1 antibodies were used at a 1:750 dilution in Western blot analysis and at a 1:100 dilution in immunohistochemistry. Gonad dissections (28) and Western blots (29) were performed as described. The anti-␣-tubulin antibody (Sigma, St. Louis, MO) was diluted 1:20,000, and Mab-414 (Berkeley Antibody, Richmond, CA) was diluted 1:400.…”

Section: Methodsmentioning

confidence: 99%

The GLD-2 poly(A) polymerase activates gld-1 mRNA in the Caenorhabditis elegans germ line

Suh¹,

Jedamzik

Eckmann

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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116

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mRNA regulation is crucial for many aspects of metazoan development and physiology, including regulation of stem cells and synaptic plasticity. In the nematode germ line, RNA regulators control stem cell maintenance, the sperm͞oocyte decision, and progression through meiosis. Of particular importance to this work are three GLD (germ-line development) regulatory proteins, each of which promotes entry into the meiotic cell cycle: GLD-1 is a STAR͞Quaking translational repressor, GLD-2 is a cytoplasmic poly(A) polymerase, and GLD-3 is a homolog of Bicaudal-C. Here we report that the gld-1 mRNA is a direct target of the GLD-2 poly(A) polymerase: polyadenylation of gld-1 mRNA depends on GLD-2, the abundance of GLD-1 protein is dependent on GLD-2, and the gld-1 mRNA coimmunoprecipitates with both GLD-2 and GLD-3 proteins. We suggest that the GLD-2 poly(A) polymerase enhances entry into the meiotic cell cycle at least in part by activating GLD-1 expression. The importance of this conclusion is twofold. First, the activation of gld-1 mRNA by GLD-2 identifies a positive regulatory step that reinforces the decision to enter the meiotic cell cycle. Second, gld-1 mRNA is initially repressed by FBF (for fem-3 binding factor) to maintain stem cells but then becomes activated by the GLD-2 poly(A) polymerase once stem cells begin to make the transition into the meiotic cell cycle. Therefore, a molecular switch regulates gld-1 mRNA activity to accomplish the transition from mitosis to meiosis. cytoplasmic poly(A) polymerase ͉ RNA regulation ͉ mitosis͞meiosis decision

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Section: Methodsmentioning

confidence: 99%

The GLD-2 poly(A) polymerase activates gld-1 mRNA in the Caenorhabditis elegans germ line

Suh¹,

Jedamzik

Eckmann

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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116

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“…In C. elegans, the ERK (MPK-1) cascade is shown to be involved in germ line development (14), and lip-1 is also required for the normal extent of germ line proliferation (19). It has also been shown that the life span of C. elegans can be extended by a mutation that prevents germ line development (20).…”

Section: Elegans Erk-mapk Cascade Promotes Longevity-in Cmentioning

confidence: 99%

The ERK-MAPK Pathway Regulates Longevity through SKN-1 and Insulin-like Signaling in Caenorhabditis elegans

Okuyama

Inoue

Ookuma

et al. 2010

Journal of Biological Chemistry

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It has not been determined yet whether the ERK-MAPK pathway regulates longevity of metazoans. Here, we show that the Caenorhabditis elegans ERK cascade promotes longevity through the two longevity-promoting transcription factors, SKN-1 and DAF-16. We find that RNAi of three genes, which constitute the ERK cascade (lin-45/RAF1, mek-2/MEK1/2, and mpk-1/ERK1/2), results in reduction of life span. Moreover, RNAi of lip-1, the gene encoding a MAPK phosphatase that inactivates MPK-1, increases life span. Epistasis analyses show that the ERK (MPK-1) cascade-mediated life span extension requires SKN-1, whose function is mediated, at least partly, through DAF-2/DAF-16 insulin-like signaling. MPK-1 phosphorylates SKN-1 on the key sites that are required for SKN-1 nuclear accumulation. Our results also show that one mechanism by which SKN-1 regulates insulin-like signaling is through the regulation of expression of insulin-like peptides. Our findings thus identify a novel ERK-MAPK-mediated signaling pathway that promotes longevity.Recent genetic studies in a variety of model organisms are beginning to reveal the signal transduction networks capable of regulating life span. The insulin-like signaling pathway plays a central role in these networks. In Caenorhabditis elegans, the FOXO transcription factor DAF-16 is required for life span extension by a mutation in daf-2, the insulin-like receptor (1-3). Recently, the longevity-promoting transcription factor SKN-1 has been shown to be inhibited by the insulin-like signaling pathway (4). However, it has not been fully elucidated how the insulin-like signaling pathway interacts with the other distinct signaling pathways to regulate longevity.The ERK-MAPK cascades are evolutionarily conserved signaling modules in eukaryotic cells and transduce signals from the cell surface to the nucleus. These cascades control diverse cellular processes, such as cell proliferation and differentiation (5-8). It has also been demonstrated that increasing nuclear ERK activity can extend replicative life span of diploid human cells (9). Furthermore, a recent report has shown that the increase in life span in mice lacking type 5 adenylyl cyclase correlates with increased ERK-MAPK signaling and that overexpression of mammalian ERK2 increases the chronological life span of yeast (10). However, it has not been determined yet whether the ERK-MAPK cascade promotes longevity of metazoans. In addition, molecular mechanisms by which ERK signaling regulates longevity have remained unclear. Here, we show that the ERK (MPK-1) cascade functions to extend life span in C. elegans. Our analyses show that ERK signaling acts through SKN-1 to regulate the DAF-2/DAF-16 insulin-like signaling and that MPK-1 phosphorylates SKN-1 on the key sites that are required for SKN-1 nuclear accumulation. Moreover, our data suggest that SKN-1 is involved in the regulation of life span through repression of expression of insulin-like peptides. Thus, our results demonstrate a role of the ERK signaling pathway in extending longevity a...

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“…FBF-1 and FBF-2 are 91% identical in amino acid sequence, have similar RNAbinding specificity, and overlap functionally (8,(23)(24)(25)(26)(27); they are referred to collectively as FBF. Eight mRNA targets of FBF have been identified using a combination of in vitro binding, physical association in worm extracts, immunocytochemistry, and genetics (5,8,(23)(24)(25)(26)(27). FBF is required for maintenance of germline stem cells, a conserved function of PUF proteins (1).…”

mentioning

confidence: 99%

Structural basis for specific recognition of multiple mRNA targets by a PUF regulatory protein

Wang

Opperman

Wickens

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Caenorhabditis elegans fem-3 binding factor (FBF) is a founding member of the PUMILIO/FBF (PUF) family of mRNA regulatory proteins. It regulates multiple mRNAs critical for stem cell maintenance and germline development. Here, we report crystal structures of FBF in complex with 6 different 9-nt RNA sequences, including elements from 4 natural mRNAs. These structures reveal that FBF binds to conserved bases at positions 1-3 and 7-8. The key specificity determinant of FBF vs. other PUF proteins lies in positions 4 -6. In FBF/RNA complexes, these bases stack directly with one another and turn away from the RNA-binding surface. A short region of FBF is sufficient to impart its unique specificity and lies directly opposite the flipped bases. We suggest that this region imposes a flattened curvature on the protein; hence, the requirement for the additional nucleotide. The principles of FBF/RNA recognition suggest a general mechanism by which PUF proteins recognize distinct families of RNAs yet exploit very nearly identical atomic contacts in doing so.crystal structure ͉ RNA ͉ translational regulation ͉ fem-3 binding factor ͉ base flipping

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LIP-1 phosphatase controls the extent of germline proliferation in Caenorhabditis elegans

Cited by 70 publications

References 37 publications

The GLD-2 poly(A) polymerase activates gld-1 mRNA in the Caenorhabditis elegans germ line

The GLD-2 poly(A) polymerase activates gld-1 mRNA in the Caenorhabditis elegans germ line

The ERK-MAPK Pathway Regulates Longevity through SKN-1 and Insulin-like Signaling in Caenorhabditis elegans

Structural basis for specific recognition of multiple mRNA targets by a PUF regulatory protein

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