A genetic interactome of the let-7 microRNA in C. elegans

Rausch, Magdalene; Ecsedi, Matyas; Bartake, Hrishikesh; Müllner, Almuth Elise; Großhans, Helge

doi:10.1016/j.ydbio.2015.02.013

Cited by 17 publications

(16 citation statements)

References 57 publications

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“…Cells in the epidermis arrest proliferation and terminally differentiate in late L4. This coincides with high expression of CKI-1 CIP/KIP and reduced expression of CDK-1, as well as other cell cycle regulators (Hong et al 1998; Rausch et al 2015). let-7 has been implicated in the repression of CDK-1, while upregulation of cki-1 was shown to depend on LIN-29 and its transcriptional cofactor MAB-10 NAB (Harris and Horvitz 2011).…”

Section: The Regulation Of Cell Cycle Progression During Developmentmentioning

confidence: 80%

Developmental Control of the Cell Cycle: Insights from Caenorhabditis elegans

Kipreos

Heuvel

2019

Genetics

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During animal development, a single fertilized egg forms a complete organism with tens to trillions of cells that encompass a large variety of cell types. Cell cycle regulation is therefore at the center of development and needs to be carried out in close coordination with cell differentiation, migration, and death, as well as tissue formation, morphogenesis, and homeostasis. The timing and frequency of cell divisions are controlled by complex combinations of external and cell-intrinsic signals that vary throughout development. Insight into how such controls determine in vivo cell division patterns has come from studies in various genetic model systems. The nematode Caenorhabditis elegans has only about 1000 somatic cells and approximately twice as many germ cells in the adult hermaphrodite. Despite the relatively small number of cells, C. elegans has diverse tissues, including intestine, nerves, striated and smooth muscle, and skin. C. elegans is unique as a model organism for studies of the cell cycle because the somatic cell lineage is invariant. Somatic cells divide at set times during development to produce daughter cells that adopt reproducible developmental fates. Studies in C. elegans have allowed the identification of conserved cell cycle regulators and provided insights into how cell cycle regulation varies between tissues. In this review, we focus on the regulation of the cell cycle in the context of C. elegans development, with reference to other systems, with the goal of better understanding how cell cycle regulation is linked to animal development in general.

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Section: The Regulation Of Cell Cycle Progression During Developmentmentioning

confidence: 80%

Developmental Control of the Cell Cycle: Insights from Caenorhabditis elegans

Kipreos

Heuvel

2019

Genetics

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“…Most did not test other genes as redundancy is assumed to be absent. The issue of redundant control is unsettled even for the same miRNA (let -7) and the same phenotype (vulva rupture) in the same species (C. elegans) (Hunter et al 2013;Ecsedi et al 2015;Rausch et al 2015). Hunter et al (2013) concluded that a large number of target genes (more than 20) participate in vulva regulation using RNAi rescue for a large panel of target genes.…”

Section: Discussionmentioning

confidence: 99%

Redundant and incoherent regulations of multiple phenotypes suggest microRNAs’ role in stability control

et al. 2017

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Each microRNA (miRNA) represses a web of target genes and, through them, controls multiple phenotypes. The difficulties inherent in such controls cast doubt on how effective miRNAs are in driving phenotypic changes. A "simple regulation" model posits "one target-one phenotype" control under which most targeting is nonfunctional. In an alternative "coordinate regulation" model, multiple targets are assumed to control the same phenotypes coherently, and most targeting is functional. Both models have some empirical support but pose different conceptual challenges. Here, we concurrently analyze multiple targets and phenotypes associated with the miRNA-310 family (miR310s) of Phenotypic rescue in the knockout background is achieved by promoter-directed RNA interference that restores wild-type expression. For one phenotype (eggshell morphology), we observed redundant regulation, hence rejecting "simple regulation" in favor of the "coordinate regulation" model. For other phenotypes (egg-hatching and male fertility), however, one gene shows full rescue, but three other rescues aggravate the phenotype. Overall, phenotypic controls by miR310s do not support either model. Like a thermostat that controls both heating and cooling elements to regulate temperature, redundancy and incoherence in regulation generally suggest some capacity in stability control. Our results therefore support the published view that miRNAs play a role in the canalization of transcriptome and, hence, phenotypes.

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“…In the case of Caenorhabditis elegans , one can perform genetic interaction screens by using an ordered library of RNAi‐inducing reagents. A number of studies have been performed using this strategy to search for genetic interactions with a range of different query mutations (Lehner et al ., ; Byrne et al ., ; Fievet et al ., ; Rausch et al ., ). A recent survey of these C .…”

Section: Introductionmentioning

confidence: 97%

“…In the case of Caenorhabditis elegans, one can perform genetic interaction screens by using an ordered library of RNAi-inducing reagents. A number of studies have been performed using this strategy to search for genetic interactions with a range of different query mutations (Lehner et al, 2006;Byrne et al, 2007;Fievet et al, 2013;Rausch et al, 2015). A recent survey of these C. elegans genetic interaction studies indicated that there have been approximately 1500 genetic interactions reported for this model organism (Boucher et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

A double‐mutant collection targeting MAP kinase related genes in Arabidopsis for studying genetic interactions

Krysan

2016

The Plant Journal

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Mitogen-activated protein kinase cascades are conserved in all eukaryotes. In Arabidopsis thaliana there are approximately 80 genes encoding MAP kinase kinase kinases (MAP3K), 10 genes encoding MAP kinase kinases (MAP2K), and 20 genes encoding MAP kinases (MAPK). Reverse genetic analysis has failed to reveal abnormal phenotypes for a majority of these genes. One strategy for uncovering gene function when single-mutant lines do not produce an informative phenotype is to perform a systematic genetic interaction screen whereby double-mutants are created from a large library of single-mutant lines. Here we describe a new collection of 275 double-mutant lines derived from a library of single-mutants targeting genes related to MAP kinase signaling. To facilitate this study, we developed a high-throughput double-mutant generating pipeline using a system for growing Arabidopsis seedlings in 96-well plates. A quantitative root growth assay was used to screen for evidence of genetic interactions in this double-mutant collection. Our screen revealed four genetic interactions, all of which caused synthetic enhancement of the root growth defects observed in a MAP kinase 4 (MPK4) single-mutant line. Seeds for this double-mutant collection are publicly available through the Arabidopsis Biological Resource Center. Scientists interested in diverse biological processes can now screen this double-mutant collection under a wide range of growth conditions in order to search for additional genetic interactions that may provide new insights into MAP kinase signaling.

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A genetic interactome of the let-7 microRNA in C. elegans

Cited by 17 publications

References 57 publications

Developmental Control of the Cell Cycle: Insights from Caenorhabditis elegans

Developmental Control of the Cell Cycle: Insights from Caenorhabditis elegans

Redundant and incoherent regulations of multiple phenotypes suggest microRNAs’ role in stability control

A double‐mutant collection targeting MAP kinase related genes in Arabidopsis for studying genetic interactions

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