MEX-3 proteins: recent insights on novel post-transcriptional regulators

Pereira, Bruno; Borgne, Maïlys Le; Chartier, Nicolas T.; Billaud, Marc; Almeida, Raquel

doi:10.1016/j.tibs.2013.08.004

Cited by 37 publications

(49 citation statements)

References 10 publications

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“…Since their initial description, several reports have sustained the idea that mammalian MEX-3 proteins play several roles in the control of RNA metabolism (Pereira et al, 2013a). MEX3A and MEX3B proteins localize in P-bodies and stress granules, two structures involved in the storage and turnover of mRNAs (BuchetPoyau et al, 2007;Courchet et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

The RNA-binding protein Mex3b regulates the spatial organization of the Rap1 pathway

et al. 2014

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The four related mammalian MEX-3 RNA-binding proteins are evolutionarily conserved molecules for which the in vivo functions have not yet been fully characterized. Here, we report that male mice deficient for the gene encoding Mex3b are subfertile. Seminiferous tubules of Mex3b-deficient mice are obstructed as a consequence of the disrupted phagocytic capacity of somatic Sertoli cells. In addition, both the formation and the integrity of the blood-testis barrier are compromised owing to mislocalization of N-cadherin and connexin 43 at the surface of Sertoli cells. We further establish that Mex3b acts to regulate the cortical level of activated Rap1, a small G protein controlling phagocytosis and cell-cell interaction, through the activation and transport of Rap1GAP. The active form of Rap1 (Rap1-GTP) is abnormally increased at the membrane cortex and chemically restoring Rap1-GTP to physiological levels rescues the phagocytic and adhesion abilities of Sertoli cells. Overall, these findings implicate Mex3b in the spatial organization of the Rap1 pathway that orchestrates Sertoli cell functions.

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Section: Introductionmentioning

confidence: 99%

The RNA-binding protein Mex3b regulates the spatial organization of the Rap1 pathway

et al. 2014

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“…MEX‐3 was first identified as a translational repressor in nematode Caenorhabditis elegans. C. elegans MEX‐3 protein is a regulator of translation that specifies the posterior blastomere identity during early embryogenesis and contributes to the maintenance of germline totipotency, immune responses, differentiation, and cancer . In mammals, there are four MEX‐3 proteins which are thought to play same roles with that of the C. elegans MEX‐3 .…”

Section: Discussionmentioning

confidence: 99%

“…C. elegans MEX-3 protein is a regulator of translation that specifies the posterior blastomere identity during early embryogenesis and contributes to the maintenance of germline totipotency, immune responses, differentiation, and cancer. 8,[12][13][14][15]29 In mammals, there are four MEX-3 proteins which are thought to play same roles with that of the C. elegans MEX-3. 15 HLA-A2 mRNA, therefore, modulating natural killer cell activity.…”

Section: Discussionmentioning

confidence: 99%

“…Human MEX‐3 protein, belonging to a novel subfamily of evolutionarily conserved RNA binding proteins, is the human homologs of Caenorhabditis elegans MEX‐3 and involved in the post‐transcriptional regulation . There are four human MEX‐3 proteins including MEX‐3A, MEX‐3B, MEX‐3C, and MEX‐3D.…”

Section: Introductionmentioning

confidence: 99%

“…6,7 Human MEX-3 protein, belonging to a novel subfamily of evolutionarily conserved RNA binding proteins, is the human homologs of Caenorhabditis elegans MEX-3 and involved in the post-transcriptional regulation. 8 There are four human MEX-3 proteins including MEX-3A, MEX-3B, MEX-3C, and MEX-3D. Each contains two heterogeneous nuclear ribonucleoprotein K homology (KH) domains at the N-terminus and an ubiquitin E3 ligase Ring finger domain at the C-terminus.…”

Section: Introductionmentioning

confidence: 99%

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Structural and functional characterization of hMEX‐3C Ring finger domain as an E3 ubiquitin ligase

et al. 2018

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MEX‐3C, a novel RNA binding E3 ubiquitin ligases, contains two N‐terminal heterogeneous nuclear ribonucleoprotein K homology (KH) domains and C‐terminal Ring finger domain. Recent evidence has suggested that human MEX‐3C has a strong bondage with carcinogenesis and the MEX‐3C‐mediated ubiquitination of RIG‐I is essential for the antiviral innate immune response. Moreover, the Ring finger domain of MEX‐3C could regulate the degradation of HLA‐A2 (an MHC‐I allotype) mRNA with a novel mechanism. However, the structural basis for the ubiquitination catalyzed by hMEX‐3C Ring finger domain remains evasive. In this study, we solved the crystal structure of dimeric Ring finger domain of hMEX‐3C and compared it with the complex structure of MDM2/MDMX–UbcH5b–Ub. Our ubiquitination assay demonstrated that the Ring finger domain of hMEX‐3C acts as a ubiquitin E3 ligase in vitro, cooperating with specific E2 to mediate ubiquitination. Then, we identified several key residues in Ring finger domain of hMEX‐3C possibly involved in the interaction with E2–Ub conjugate and analyzed the E3 ligase activities of wild type and mutants at key sites. Additionally, zinc chelation experiments indicated that the intact structural stability is essential for the self‐ubiquitination activity of the Ring finger domain of hMEX‐3C. Taken together, our studies provided new insight into the mechanism of the Ring finger domain of hMEX‐3C that may play an important role in eliciting antiviral immune responses and therapeutic interventions.

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The multipotency‐to‐commitment transition in Caenorhabditis elegans—implications for reprogramming from cells to organs

2018

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In animal embryos, cells transition from a multipotential state, with the capacity to adopt multiple fates, into an irreversible, committed state of differentiation. This multipotency-to-commitment transition (MCT) is evident from experiments in which cell fate is reprogrammed by transcription factors for cell type-specific differentiation, as has been observed extensively in Caenorhabditis elegans. Although factors that direct differentiation into each of the three germ layer types cannot generally reprogram cells after the MCT in this animal, transcription factors for endoderm development are able to do so in multiple differentiated cell types. In one case, these factors can redirect the development of an entire organ in the process of "transorganogenesis". Natural transdifferentiation also occurs in a small number of differentiated cells during normal C. elegans development. We review these reprogramming and transdifferentiation events, highlighting the cellular and developmental contexts in which they occur, and discuss common themes underlying direct cell lineage reprogramming. Although certain aspects may be unique to the model system, growing evidence suggests that some mechanisms are evolutionarily conserved and may shed light on cellular plasticity and disease in humans.

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MEX-3 proteins: recent insights on novel post-transcriptional regulators

Cited by 37 publications

References 10 publications

The RNA-binding protein Mex3b regulates the spatial organization of the Rap1 pathway

The RNA-binding protein Mex3b regulates the spatial organization of the Rap1 pathway

Structural and functional characterization of hMEX‐3C Ring finger domain as an E3 ubiquitin ligase

The multipotency‐to‐commitment transition in Caenorhabditis elegans—implications for reprogramming from cells to organs

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