The RabGAP TBC-11 controls Argonaute localization for proper microRNA function in C. elegans

Michaud, Pascale; Shah, Vivek Nilesh; Adjibade, Pauline; Houle, François; Huberdeau, Miguel Quévillon; Rioux, Rachel; Lavoie-Ouellet, Camille; Gu, Weifeng; Mazrouï, Rachid; Simard, Martin J.

doi:10.1371/journal.pgen.1009511

Cited by 7 publications

(4 citation statements)

References 51 publications

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“…Importantly, emerging evidence has verified that miR-NAs modulate the expression of mRNAs by base pairing with the 3′UTR of mRNAs to silence their translation or degrade them [24][25][26]. To identify the downstream target of miR-4284, four potential mRNAs with binding sites on miR-4284 sequence were predicted by miRDB website and based on a series of assays, DNA meiotic recombinase 1 (DMC1) was confirmed to be the target mRNA.…”

Section: Discussionmentioning

confidence: 99%

MiR-4284 inhibits sensitivity to paclitaxel in human ovarian carcinoma SKOV3ip1 and HeyA8 cells by targeting DMC1

Shang¹,

Pan²,

Jiang

et al. 2022

Anti-Cancer Drugs

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An increasing number of studies have confirmed that microRNAs (miRNAs) are involved in various biological processes, including tumor growth and drug resistance. MiR-4284 has been proved to be abnormally regulated in several cancers, but the function of miR-4284 in ovarian carcinoma (OC) is unclear. Paclitaxel resistance is a key obstacle in OC treatment. Here, the role of miR-4284 in cell sensitivity to paclitaxel in OC was investigated. Two OC cell lines (SKOV3ip1 and HeyA8) were utilized for the establishment of paclitaxel-resistant cell lines. Reverse transcription-quantitative PCR (RT-qPCR) was applied to analyze the levels of miR-4284 and potential mRNAs in OC cell lines. Western blotting was performed to evaluate the levels of DNA meiotic recombinase 1 (DMC1) protein and cell cycle-associated proteins. Identification of the relationship between miR-4284 and DMC1 was achieved by luciferase reporter assay. CCK-8 and flow cytometry assays were utilized for evaluating the impact of miR-4284 on the malignant characteristics of paclitaxel-resistant OC cells. MiR-4284 was upregulated in paclitaxel-resistant OC cell lines and correlated with an adverse prognosis in OC patients. Depletion of miR-4284 suppressed cell proliferation and cell cycle progression of paclitaxel-resistant OC. MiR-4284 targeted DMC1 which was downregulated in paclitaxel-resistant cells and reversed the inhibitory influence of miR-4284 silencing on the malignant characters of paclitaxel-resistant OC cells. MiR-4284 targets DMC1 to suppress sensitivity to paclitaxel in human OC cells.

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Section: Discussionmentioning

confidence: 99%

MiR-4284 inhibits sensitivity to paclitaxel in human ovarian carcinoma SKOV3ip1 and HeyA8 cells by targeting DMC1

Shang¹,

Pan²,

Jiang

et al. 2022

Anti-Cancer Drugs

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“…This cuticle structure is generated by seam cells at the L4 to adult transition. The proper timing and differentiation of seam cells in larval development requires specific miRNAs, including lin-4 and let-7 miRNA family (33,47,(51)(52)(53)(54). The alteration of miRNA function in the process leads to an abnormal number and defective fusion of seam cells, causing incomplete alae breaks along the structure (55)(56)(57).…”

Section: The Slicing Activity Of Alg-1 and Alg-2 Contributes To Mirna...mentioning

confidence: 99%

“…To specifically determine the role of the slicing activity of ALG-1 and ALG-2 in the miRNA function, we focus on phenotypes known to be affected by the alteration of this regulatory pathways in C .elegans. Among the developmental processes controlled by miRNAs, the alae is a cuticle structure, generated by the seam cells at the L4 to adult transition for which the proper timing and differentiation of these cells, during larval development, requires specific miRNAs, including lin-4 and let-7 miRNA family (34,(50)(51)(52)(53)(54). Any alteration of these miRNA functions would affect their number or cause defective fusion of these seam cells, leading to phenotypical incomplete alae breaks along the structure (55)(56)(57).…”

Section: The Slicing Activity Of Alg-1 and Alg-2 Pleiotropically Infl...mentioning

confidence: 99%

Defining the contribution of microRNA-specific slicing Argonautes in animals

Pal

Vasudevan

Houle

et al. 2023

Preprint

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microRNAs regulate gene expression through interaction with an Argonaute protein family member. While some members of this protein family retain an enzymatic activity capable of cleaving RNA molecules complementary to Argonaute-bound small RNAs, the role of the slicing activity in the canonical microRNA pathway is still unclear in animals. To address the importance of slicing Argonautes in animals, we createdCaenorhabditis elegansmutant strains carrying catalytically dead endogenous ALG-1 and ALG-2, the only two slicing Argonautes essential for the miRNA pathway in this animal model. We observe that the loss of ALG-1 and ALG-2 slicing activity affects overall animal fitness and causes phenotypes reminiscent of miRNA defects only when grown and maintained at restrictive temperature. Furthermore, the analysis of global miRNA expression show that the catalytic activity of ALG-1 and ALG-2 differentially regulate the level of specific subsets of miRNAs in young adults. We also demonstrate that altering the slicing activity of those miRNA-specific Argonautes does not result in any defect in the production of canonical miRNAs. Together, these data support that the slicing activity of miRNA-specific Argonautes functions to maintain levels of a set of miRNAs for optimal viability and fitness in animals particularly exposed to specific growing conditions.

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“…Also, an in vivo study in C. elegans suggests that the RAB‐6 small GTPase pathway can regulate miRISC function by modulating the cellular distribution of AGO ALG‐1 and its association to miRNA. More specifically, altering the RAB‐6 pathway caused the accumulation of ALG‐1 in a high molecular weight complex localized at the perinuclear region of the cell (Michaud et al, 2021) (Figure 5).…”

Section: Modifications and Modulation Of The Miriscmentioning

confidence: 99%

Regulation and different functions of the animal microRNA‐induced silencing complex

Frédérick

Simard

2021

WIREs RNA

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Among the different types of small RNAs, microRNAs (miRNAs) are key players in controlling gene expression at the mRNA level. To be active, they must associate with an Argonaute protein to form the miRNA induced silencing complex (miRISC) and binds to specific mRNA through complementarity sequences. The miRISC binding to an mRNA can lead to multiple outcomes, the most frequent being inhibition of the translation and/or deadenylation followed by decapping and mRNA decay. In the last years, several studies described different mechanisms modulating miRISC functions in animals. For instance, the regulation of the Argonaute protein through post-translational modifications can change the miRISC gene regulatory activity as well as modulate its binding to proteins, mRNA targets and miRISC stability. Furthermore, the presence of RNA binding proteins and multiple miRISCs at the targeted mRNA 3 0 untranslated region (3 0 UTR) can also affect its function through cooperation or competition mechanisms, underlying the importance of the 3 0 UTR environment in miRNA-mediated repression. Another way to regulate the miRISC function is by modulation of its interactors, forming different types of miRNA silencing complexes that affect gene regulation differently. It is also reported that the subcellular localization of several components of the miRNA pathway can modulate miRISC function, suggesting an important role for vesicular trafficking in the regulation of this essential silencing complex.

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The RabGAP TBC-11 controls Argonaute localization for proper microRNA function in C. elegans

Cited by 7 publications

References 51 publications

MiR-4284 inhibits sensitivity to paclitaxel in human ovarian carcinoma SKOV3ip1 and HeyA8 cells by targeting DMC1

MiR-4284 inhibits sensitivity to paclitaxel in human ovarian carcinoma SKOV3ip1 and HeyA8 cells by targeting DMC1

Defining the contribution of microRNA-specific slicing Argonautes in animals

Regulation and different functions of the animal microRNA‐induced silencing complex

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