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Endogenous transcripts direct microRNA degradation in Drosophila, and this targeted degradation is required for proper embryonic development

ABSTRACT: Endogenous transcripts direct microRNA degradation in Drosophila, and this targeted degradation is required for proper embryonic development

PROVIDER: PRJNA807525 | ENA |

REPOSITORIES: ENA

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Endogenous transcripts direct microRNA degradation in Drosophila, and this targeted degradation is required for proper embryonic development

Project description:MicroRNAs (miRNAs) typically direct degradation of their mRNA targets. However, five miRNA targets in vertebrate animals are reported to have unusual miRNA-binding sites that direct degradation of cognate miRNAs. Here, we identify six sites, five in mRNAs and one in a non-coding RNA named Marge, that serve this purpose in Drosophila cells or embryos, which shows that target-directed miRNA degradation (TDMD) shapes endogenous miRNA levels in some invertebrate animals. The six sites direct miRNA degradation without collateral target degradation, helping to explain the potency of this miRNA-degradation pathway. Mutations that disrupt this pathway in Drosophila are lethal, with many flies dying as embryos. Derepression of miR-3 and its paralog miR-309 is responsible for some of this lethality, whereas the loss of Marge-directed degradation of miR-310 miRNAs causes defects in embryonic cuticle development. Thus, TDMD is strongly implicated in the viability of an animal and is required for its proper development.

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Novel endogenous antisense transcripts in mouse

Project description:This SuperSeries is composed of the following subset Series: GSE14372: Novel endogenous antisense transcripts (data for the mouse normal tissues) GSE14557: Novel endogenous antisense transcripts (data for the mouse mammary tumors) Refer to individual Series Unpublished data has been masked in the supplementary feature extraction files.

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Endogenous transcripts control miRNA levels and activity in mammalian cells by a target-dependent miRNA degradation mechanism

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Endogenous transcripts control miRNA levels and activity in mammalian cells by a target-dependent miRNA degradation mechanism [RNA-Seq_2]

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Endogenous transcripts control miRNA levels and activity in mammalian cells by a target-dependent miRNA degradation mechanism [miRNA-Seq]

Project description:Endogenous transcripts control miRNA levels and activity in mammalian cells by a target-dependent miRNA degradation mechanism [miRNA-Seq]

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Endogenous transcripts control miRNA levels and activity in mammalian cells by a target-dependent miRNA degradation mechanism [RNA-Seq]

Project description:Endogenous transcripts control miRNA levels and activity in mammalian cells by a target-dependent miRNA degradation mechanism [RNA-Seq]

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Endogenous transcripts control miRNA levels and activity in mammalian cells by a target-dependent miRNA degradation mechanism [RNA-Seq_2]

Project description:Little is known about how miRNAs are turned over, in particular in mammalian cells. A target-dependent miRNA degradation mechanism (TDMD) has been recently suggested, in which RNA targets may induce miRNA degradation. However, endogenous RNA targets involved in TDMD have not been yet identified. During serum stimulation of quiescent fibroblasts, a deep change of miRNA expression occurs in few hours. We scanned the mammalian genome for targets eligible for TDMD and found a dominant miRNA:target pair, consisting of a target (SerpinE1) extraordinarily induced upon serum stimulation and two matched miRNAs (miR-30b/c) quickly downregulated. We verified directly the occurrence of TDMD by interfering specifically with the miR-:target interaction, keeping target and miRNA expression at endogenous levels, using CRISPR/cas9 mediated deletion of the miR-30 responsive element (MRE) of SerpinE1. In MRE-KO cells, we observed the stabilization of the predicted miRNAs, with no evidence of alterations in precursors or unrelated miRNAs, suggesting that TDMD is occurring and has been disrupted by a single MRE deletion. At molecular level miRNA degradation occurs within physiological ranges of target expression (upon 1000 copies per cells) and is accompanied by modification on 3’ends (tailing, mostly through adenylation). TDMD suppression was sufficient to shift the activity of miR-30b/c towards other shared targets, modulate significantly gene expression and, thus, influence cellular functions, including cell proliferation, apoptosis, and adhesion. In conclusion, these data strongly support the existence of a novel and sophisticated regulatory layer of miRNA and gene expression mediated by specific endogenous targets in mammalian cells.

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Endogenous transcripts control miRNA levels and activity in mammalian cells by a target-dependent miRNA degradation mechanism [RNA-Seq]

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Endogenous transcripts control miRNA levels and activity in mammalian cells by a target-dependent miRNA degradation mechanism [miRNA-Seq]

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