miR-1 sustains muscle physiology by controlling V-ATPase complex assembly

Gutiérrez-Pérez, Paula; Santillán, Emilio M.; Lendl, Thomas; Wang, Jingkui; Schrempf, Anna; Steinacker, Thomas L.; Asparuhova, Mila; Brandstetter, Marlene; Haselbach, David; Cochella, Luisa

doi:10.1126/sciadv.abh1434

Cited by 15 publications

(20 citation statements)

References 85 publications

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“…The RabGAP tbc-7 has been previously reported to be regulated by mir-1 [ 21 , 29 ], whereby mir-1 binds directly to the 3’UTR of tbc-7 to silence its expression. The loss of the mir-1 binding site or the loss of mir-1 itself results in an overexpression of tbc-7 , causing impaired autophagy and proteotoxic stress [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

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Germline stem cell integrity and quiescence are controlled by an AMPK-dependent neuronal trafficking pathway

et al. 2023

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During periods of energetic stress, Caenorhabditis elegans can execute a developmentally quiescent stage called “dauer”, during which all germline stem cells undergo a G2 cell cycle arrest. In animals that lack AMP-activated protein kinase (AMPK) signalling, the germ cells fail to arrest, undergo uncontrolled proliferation, and lose their reproductive capacity upon recovery from this quiescent stage. These germline defects are accompanied by, and likely result from, an altered chromatin landscape and gene expression program. Through genetic analysis we identified an allele of tbc-7, a predicted RabGAP protein that functions in the neurons, which when compromised, suppresses the germline hyperplasia in the dauer larvae, as well as the post-dauer sterility and somatic defects characteristic of AMPK mutants. This mutation also corrects the abundance and aberrant distribution of transcriptionally activating and repressive chromatin marks in animals that otherwise lack all AMPK signalling. We identified RAB-7 as one of the potential RAB proteins that is modulated by tbc-7 and show that the activity of RAB-7 is critical for the maintenance of germ cell integrity during the dauer stage. We reveal that TBC-7 is regulated by AMPK through two mechanisms when the animals enter the dauer stage. Acutely, the AMPK-mediated phosphorylation of TBC-7 reduces its activity, potentially by autoinhibition, thereby preventing the inactivation of RAB-7. In the more long term, AMPK regulates the miRNAs mir-1 and mir-44 to attenuate tbc-7 expression. Consistent with this, animals lacking mir-1 and mir-44 are post-dauer sterile, phenocopying the germline defects of AMPK mutants. Altogether, we have uncovered an AMPK-dependent and microRNA-regulated cellular trafficking pathway that is initiated in the neurons, and is critical to control germline gene expression cell non-autonomously in response to adverse environmental conditions.

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Section: Resultsmentioning

confidence: 99%

“…The RabGAP tbc-7 has been previously reported to be regulated by mir-1 [21,29], whereby mir-1 binds directly to the 3'UTR of tbc-7 to silence its expression. The loss of the mir-1…”

Section: Mir-1 and Mir-44 Negatively Regulate Tbc-7 Downstream Of Amp...mentioning

confidence: 99%

Germline stem cell integrity and quiescence are controlled by an AMPK-dependent neuronal trafficking pathway

et al. 2023

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“…To understand how this is occurring, the prime example is the role of mir-1 in the developing muscle tissue. Both the miR-1 ( mir-1 in the worm) sequence and its function in the developing muscle tissue are highly conserved in flies, worms, and mammals [ 124 , 125 , 126 ]. In Drosophila miR-1 is expressed in mesodermal cells and, by the larval stages, many muscle cells, including somatic, visceral, and pharyngeal muscle cells [ 124 ].…”

Section: Mirnas In Larval Developmentmentioning

confidence: 99%

A Compilation of the Diverse miRNA Functions in Caenorhabditis elegans and Drosophila melanogaster Development

Quesnelle

Bendena

Chin-Sang

2023

IJMS

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MicroRNAs are critical regulators of post-transcriptional gene expression in a wide range of taxa, including invertebrates, mammals, and plants. Since their discovery in the nematode, Caenorhabditis elegans, miRNA research has exploded, and they are being identified in almost every facet of development. Invertebrate model organisms, particularly C. elegans, and Drosophila melanogaster, are ideal systems for studying miRNA function, and the roles of many miRNAs are known in these animals. In this review, we compiled the functions of many of the miRNAs that are involved in the development of these invertebrate model species. We examine how gene regulation by miRNAs shapes both embryonic and larval development and show that, although many different aspects of development are regulated, several trends are apparent in the nature of their regulation.

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“…miRNA targets are recognized by sequence complementarity, with most known targets in animals exhibiting a perfect complementarity to the miRNA “seed” sequence (nt 2–7), and imperfect complementarity to the rest of the miRNA sequence [Bartel, 2018]. While computational tools, and high-throughput molecular biology methods, typically predict hundreds of RNA targets for each miRNA, in vivo genetics usually identifies just a few key targets responsible for miRNA-controlled phenotypes [Seitz, 2009 ; Ecsedi et al, 2015 ; Title et al, 2018 ; Aeschimann et al, 2019 ; Gutiérrez-Pérez et al, 2021].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of microRNA variant maturation prior to genome edition

Busseau

Mockly

Houbron

et al. 2022

Preprint

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Assessment of the functionality of individual microRNA/target sites is a crucial issue. Genome editing techniques should theoretically permit a fine functional exploration of such interactions, allowing the mutation of microRNAs or individual binding sites in a complete in vivo setting, therefore abrogating or restoring individual interactions on demand. A major limitation to this experimental strategy is the influence of microRNA sequence on its accumulation level, which introduces a confounding effect when assessing phenotypic rescue by compensatorily mutated microRNA and target site. Here we describe a simple assay to identify microRNA variants most likely to accumulate at wild-type levels even though their sequence has been mutated. In this assay, quantification of a reporter construct in cultured cells predicts the efficiency of an early biogenesis step, the Drosha-dependent cleavage of microRNA precursors, which appears to be a major determinant of microRNA accumulation in our variant collection. This system allowed the generation of a mutant Drosophila strain expressing a bantam microRNA variant at wild-type levels.

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miR-1 sustains muscle physiology by controlling V-ATPase complex assembly

Cited by 15 publications

References 85 publications

Germline stem cell integrity and quiescence are controlled by an AMPK-dependent neuronal trafficking pathway

Germline stem cell integrity and quiescence are controlled by an AMPK-dependent neuronal trafficking pathway

A Compilation of the Diverse miRNA Functions in Caenorhabditis elegans and Drosophila melanogaster Development

Evaluation of microRNA variant maturation prior to genome edition

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