Developmental Characterization of the MicroRNA-Specific C. elegans Argonautes alg-1 and alg-2

Vasquez-Rifo, Alejandro; Jannot, Guillaume; Armisen, Javier; Labouesse, Michel; Bukhari, Syed Irfan Ahmad; Rondeau, Evelyne L.; Miska, Eric A.; Simard, Martin J.

doi:10.1371/journal.pone.0033750

Cited by 70 publications

(99 citation statements)

References 46 publications

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“…First, tissue specific knockdown of alg-1 was performed in the cells of the somatic gonad. Expression of alg-1 and alg-2 has been analyzed extensively (Tops et al, 2006; Vasquez-Rifo et al, 2012). alg-1 is expressed from early embryogenesis to adulthood in most, if not all, cells (Tops et al, 2006) and both alg-1 and alg-2 are expressed in the cells of the somatic gonad (Vasquez-Rifo et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

Functional analysis of microRNA pathway genes in the somatic gonad and germ cells during ovulation in C. elegans

Rios

Warren

Olson

et al. 2017

Developmental Biology

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MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that play critical roles in animal development and physiology, though functions for most miRNAs remain unknown. Worms with reduced miRNA biogenesis due to loss of Drosha or Pasha/DGCR8 activity are sterile and fail to ovulate, indicating that miRNAs are required for the process of oocyte maturation and ovulation. Starting with this penetrant sterile phenotype and using new strains created to perform tissue specific RNAi, we characterize the roles of the C. elegans Pasha, pash-1, and two miRNA-specific Argonautes, alg-1 and alg-2, in somatic gonad cells and in germ cells in the regulation of ovulation. Conditional loss of pash-1 activity resulted in a reduced rate of ovulation and in basal and ovulatory sheath contractions. Similarly, knockdown of miRNA-specific Argonautes in the cells of the somatic gonad by tissue-specific RNAi results in a reduction of the ovulation rate and in basal and ovulatory sheath contractions. Reduced miRNA pathway gene activity resulted in a range of defects, including oocytes that were pinched upon entry of the oocyte into the distal end of the spermatheca in about 42% of the ovulation events observed following alg-1 RNAi. This phenotype was not observed on worms exposed to control RNAi. In contrast, knockdown of alg-1 and alg-2 in germ cells results in few defects in oocyte maturation and ovulation. These data identify specific steps in the process of ovulation that require miRNA pathway gene activity in the somatic gonad cells.

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Section: Resultsmentioning

confidence: 99%

Functional analysis of microRNA pathway genes in the somatic gonad and germ cells during ovulation in C. elegans

Rios

Warren

Olson

et al. 2017

Developmental Biology

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show abstract

“…Moreover, mature miRNAs exert their repressive function in association with a member of the Argonaute (Ago) protein family (reviewed by Iwakawa and Tomari, 2015), and the removal of this Ago effector protein has also been a useful tool for assessing the contribution of miRNA-mediated repression to different processes. For instance, in Caenorhabditis elegans, zygotic removal of both miRNA-dedicated Argonautes, ALG-1 and ALG-2, causes embryonic arrest during morphogenesis (Vasquez-Rifo et al, 2012). In mice, two Ago2 null alleles lead to developmental arrest around embryonic day (E) 5.5 or 7.5 (Alisch et al, 2007;Morita et al, 2007), and loss of Dicer1 also causes early embryonic lethality, with animals arresting before E7.5, prior to the body plan being established (Bernstein et al, 2003); however, it should be noted that Dicer is also involved in the endo siRNA pathway, so a contribution from this other class of small RNAs should be considered in the interpretation of such experiments.…”

Section: Introductionmentioning

confidence: 99%

A framework for understanding the roles of miRNAs in animal development

2017

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MicroRNAs (miRNAs) contribute to the progressive changes in gene expression that occur during development. The combined loss of all miRNAs results in embryonic lethality in all animals analyzed, illustrating the crucial role that miRNAs play collectively. However, although the loss of some individual miRNAs also results in severe developmental defects, the roles of many other miRNAs have been challenging to uncover. This has been mostly attributed to their proposed function as tuners of gene expression or providers of robustness. Here, we present a view of miRNAs in the context of development as a hierarchical and canalized series of gene regulatory networks. In this scheme, only a fraction of embryonic miRNAs act at the top of this hierarchy, with their loss resulting in broad developmental defects, whereas most other miRNAs are expressed with high cellular specificity and play roles at the periphery of development, affecting the terminal features of specialized cells. This view could help to shed new light on our understanding of miRNA function in development, disease and evolution.

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“…To ascertain whether microRNAs regulate nicotine-dependent behavior, we tested alg-1 mutant worms for acute and withdrawal responses. ALG-1, a member of the Argonaute family, is a key component of the microRNA-induced silencing complex (miRISC) and is required for microRNA activity (Vasquez-Rifo et al, 2012). We found that alg-1 mutant worms were severely defective in nicotine withdrawal (Fig.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA Regulation of nAChR Expression and Nicotine-Dependent Behavior in C. elegans

et al. 2017

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Summary Chronic exposure to nicotine up-regulates nicotinic acetylcholine receptors (nAChRs), and such up-regulation is critical for the development of nicotine dependence in humans and animal models. However, how nicotine up-regulates nAChRs is not well understood. Here we identify a key role for microRNA in regulating nicotine-dependent behavior by modulating nAChR expression in C. elegans. We show that the nAChR gene acr-19 and alg-1, a key Argonaute-family member in the microRNA machinery, are specifically required for nicotine withdrawal response following chronic nicotine treatment. Chronic exposure to nicotine down-regulates alg-1, leading to up-regulation of acr-19. This effect is mediated by the microRNA miR-238 that recognizes the 3′UTR of acr-19 transcript. Our results unveil a previously unrecognized role for microRNA in nicotine signaling, providing insights into how chronic nicotine administration leads to up-regulation of nAChR and ultimately nicotine dependence.

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Developmental Characterization of the MicroRNA-Specific C. elegans Argonautes alg-1 and alg-2

Cited by 70 publications

References 46 publications

Functional analysis of microRNA pathway genes in the somatic gonad and germ cells during ovulation in C. elegans

Functional analysis of microRNA pathway genes in the somatic gonad and germ cells during ovulation in C. elegans

A framework for understanding the roles of miRNAs in animal development

MicroRNA Regulation of nAChR Expression and Nicotine-Dependent Behavior in C. elegans

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