Genome-scale spatiotemporal analysis of <i>Caenorhabditis elegans</i> microRNA promoter activity

Martínez, Natàlia; Ow, Maria C.; Reece‐Hoyes, John S.; Barrasa, M. Inmaculada; Ambros, Victor R.; Walhout, Albertha J.M.

doi:10.1101/gr.083055.108

Cited by 203 publications

(267 citation statements)

References 60 publications

(100 reference statements)

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“…These expression patterns are in agreement with previous Northern data (Lim et al 2003). These data are also largely in agreement with a previous study of miRNA expression in C. elegans using similar GFP transgenes (Martinez et al 2008). One exception is miR-52, which is one of the most highly expressed miRNAs in C. elegans by Northern (Lim et al 2003) and high-throughput sequencing (Kato et al 2009), but was not found to be expressed strongly by promoter fusion experiments in the earlier study (Martinez et al mir-51Tgfp is expressed in anterior ventral cells (C and D, Z-projection; 10 mm), and mir-52Tgfp is ubiquitously expressed in the soma (E and F).…”

Section: Resultssupporting

confidence: 83%

The Conserved miR-51 microRNA Family Is Redundantly Required for Embryonic Development and Pharynx Attachment in Caenorhabditis elegans

et al. 2010

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microRNAs (miRNAs) are 22-nucleotide small RNAs that act as endogenous regulators of gene expression by base-pairing with target mRNAs. Here we analyze the function of the six members of the Caenorhabditis elegans miR-51 family of miRNAs (miR-51, miR-52, miR-53, miR-54, miR-55, miR-56). miR-51 family miRNAs are broadly expressed from mid-embryogenesis onward. The miR-51 family is redundantly required for embryonic development. mir-51 family mutants display a highly penetrant pharynx unattached (Pun) phenotype, where the pharyngeal muscle, the food pump of C. elegans, is not attached to the mouth. Unusually, the Pun phenotype in mir-51 family mutants is not due to a failure to attach, but instead a failure to maintain attachment during late embryogenesis. Expression of the miR-51 family in the mouth is sufficient to maintain attachment. The Fat cadherin ortholog CDH-3 is expressed in the mouth and is a direct target of the miR-51 family miRNAs. Genetic analysis reveals that miR-51 family miRNAs might act in part through CDH-3 to regulate pharynx attachment. This study is the first to assign a function to the miR-51/miR-100 miRNA family in any organism.

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Section: Resultssupporting

confidence: 83%

The Conserved miR-51 microRNA Family Is Redundantly Required for Embryonic Development and Pharynx Attachment in Caenorhabditis elegans

et al. 2010

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“…However, we were not able to explore the GFP reporter activity of let-7-Fam miRNA genes upon P. aeruginosa infection directly due to apparent nonspecific degradation of GFP (possibly caused by cellular autophagy and/ or necrosis) when animals were treated with P. aeruginosa. Additionally, it should be noted that the transcriptional regulation by p38 of let-7-Fam miRNAs could be more complex than observed here, because the reporter transgenes used in our study may not have necessarily contained all relevant regulatory elements (47).…”

Section: Discussionmentioning

confidence: 65%

Caenorhabditis elegans microRNAs of the let-7 family act in innate immune response circuits and confer robust developmental timing against pathogen stress

Ren

Ambros

2015

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

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Animals maintain their developmental robustness against natural stresses through numerous regulatory mechanisms, including the posttranscriptional regulation of gene expression by microRNAs (miRNAs). Caenorhabditis elegans miRNAs of the let-7 family (let-7-Fam) function semiredundantly to confer robust stage specificity of cell fates in the hypodermal seam cell lineages. Here, we show reciprocal regulatory interactions between let-7-Fam miRNAs and the innate immune response pathway in C. elegans. Upon infection of C. elegans larvae with the opportunistic human pathogen Pseudomonas aeruginosa, the developmental timing defects of certain let-7-Fam miRNA mutants are enhanced. This enhancement is mediated by the p38 MAPK innate immune pathway acting in opposition to let-7-Fam miRNA activity, possibly via the downstream Activating Transcription Factor-7 (ATF-7). Furthermore, let-7-Fam miRNAs appear to exert negative regulation on the worm's resistance to P. aeruginosa infection. Our results show that the inhibition of pathogen resistance by let-7 involves downstream heterochronic genes and the p38 MAPK pathway. These findings suggest that let-7-Fam miRNAs are integrated into innate immunity gene regulatory networks, such that this family of miRNAs modulates immune responses while also ensuring robust timing of developmental events under pathogen stress.let-7 family microRNAs | p38 | Pseudomonas aeruginosa | developmental timing | innate immunity D uring development, animals routinely encounter environmental, physiological, and nutritional challenges that threaten to compromise the robust execution of developmental programs. Therefore, the genetic programming of development includes mechanisms to ensure that developmental events occur flawlessly despite stressful conditions (1, 2). Several studies indicate that microRNAs (miRNAs) are used to maintain the robustness of biological processes under stress conditions (3-10). miRNAs are endogenous, noncoding, small RNAs that posttranscriptionally regulate gene expression primarily through binding to the 3′UTR of target mRNAs, which results in translation inhibition and/or mRNA degradation (11). miRNAs with the same seed sequence (nucleotides 2-7 of the mature miRNA sequence), which are predicated potentially to share the same set of targets (12), are grouped into a family.The miRNA lin-4 and the miRNAs of the let-7 family (let-7-Fam) are central to the regulation of pluripotency and differentiation in many animal systems, including mammals (13-18). Four Caenorhabditis elegans let-7-Fam miRNAs, let-7, mir-48, mir-84, and mir-241, function in concert to repress key heterochronic gene targets, including daf-12, lin-41, and hbl-1, to stagespecifically regulate the timing of the hypodermal seam cell fates (16,(19)(20)(21)(22). In C. elegans, the temporal patterns of cell division and cell fate during larval development are exquisitely invariant, even though larvae develop as free-living inhabitants of a changing environment in soil and decaying plant materials.In the wild, worms...

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“…Recently, the expression pattern of several C. elegans miRNAs has been studied in vivo using miRNA promoter::GFP fusion constructs [26]. Table S1).…”

Section: Mirnas Expressed In the Dtc Are Implicated In Germ Cell Prolmentioning

confidence: 99%

The microRNA pathway controls germ cell proliferation and differentiation in C. elegans

et al. 2012

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The discovery of the miRNA pathway revealed a new layer of molecular control of biological processes. To uncover new functions of this gene regulatory pathway, we undertook the characterization of the two miRNA-specific Argonaute proteins in Caenorhabditis elegans, ALG-1 and ALG-2. We first observed that the loss-of-function of alg-1 and alg-2 genes resulted in reduced progeny number. An extensive analysis of the germline of these mutants revealed a reduced mitotic region, indicating fewer proliferating germ cells. We also observed an early entry into meiosis in alg-1 and alg-2 mutant animals. We detected ALG-1 and ALG-2 protein expressions in the distal tip cell (DTC), a specialized cell located at the tip of both C. elegans gonadal arms that regulates mitosis-meiosis transition. Re-establishing the expression of alg-1 specifically in the DTC of mutant animals partially rescued the observed germline defects. Further analyses also support the implication of the miRNA pathway in gametogenesis. Interestingly, we observed that disruption of five miRNAs expressed in the DTC led to similar phenotypes. Finally, gene expression analysis of alg-1 mutant gonads suggests that the miRNA pathway is involved in the regulation of different pathways important for germline proliferation and differentiation. Collectively, our data indicate that the miRNA pathway plays a crucial role in the control of germ cell biogenesis in C. elegans.

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Genome-scale spatiotemporal analysis of Caenorhabditis elegans microRNA promoter activity

Cited by 203 publications

References 60 publications

The Conserved miR-51 microRNA Family Is Redundantly Required for Embryonic Development and Pharynx Attachment in Caenorhabditis elegans

The Conserved miR-51 microRNA Family Is Redundantly Required for Embryonic Development and Pharynx Attachment in Caenorhabditis elegans

Caenorhabditis elegans microRNAs of the let-7 family act in innate immune response circuits and confer robust developmental timing against pathogen stress

The microRNA pathway controls germ cell proliferation and differentiation in C. elegans

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