MNSFβ regulates placental development by conjugating IGF2BP2 to enhance trophoblast cell invasiveness

Abstract

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Maternal sterol 27-hydroxylase is crucial for securing fetal development

“…The placentas from Cyp27a1 HT mat and Cyp27a1 KO mat fetuses appeared normal (Figure 7A); however, their diameters and weights were significantly smaller than those from WT mothers (Figures 7B and C). Furthermore, histological analyses using H&E staining and immunostaining for cytokeratin 7 (CK7) (Yang et al, 2021) revealed that the labyrinth area of the placentas of Cyp27a1 KO mat fetuses was significantly thinner than that of Cyp27a1 HT mat and WT fetuses (Figures 7D-F), as reported in the Fau -deficient mice (Gu et al, 2015; Yang et al, 2021). Similar to that in the fetal lung, polysome formation in the placenta of Cyp27a1 KO mat fetuses was impaired (Figure 7G), suggesting an abnormality in translation.…”

“…Fau/Mnsfβ is highly and broadly expressed in both murine and human placenta, and Fau -deficient mice exhibit placental malformation (Gu et al, 2015; Yang et al, 2021). Moreover, a large cohort study has identified a single nucleotide polymorphism (SNP) in FAU to correlate with recurrent pregnancy loss in a Chinese Han population (Gu et al, 2018).…”

“…Of note, concentrations of specific oxysterols, including 7α-HC, are elevated in Cyp27a1 KO mice even without pregnancy (Supplementary Figure S6C and Griffiths et al, 2019); however, both male and female mice did not develop any severe phenotype unless a high-cholesterol diet was given (Rosen 1998;Sigurdsson et al, 2016). One possible reason for this is the Fau expression pattern, which is high in the placenta (Gu et al, 2015;Yang et al, 2021); therefore, its impact is limited to the fetal stage.…”

Transgenic RFP‐RPS‐30UbL strain of the nematode Caenorhabditis elegans as a biomonitor for environmental pollutants

“…RPS-30 UbL is a ubiquitin-like protein and its homologue in human functions in various biological processes by covalently binding to various target proteins, such as pro-apoptotic protein Bcl-G, phagocytosis-regulated protein endophilin II and invasion-related protein IGF2BP2. 18,19,41,42 The structure of 'beta folding grip' and the internal lysine residues, K27 and K43 in RPS-30 UbL ing Bcl-G, 18 which is a member of the Bcl-2 family of apoptosis control protein. 19 Therefore, with both the function and the structural characterization of potential modification, RPS-30 UbL might be related to the process of apoptosis induced by contaminants via accumulating to form the 'rod-like' structures.…”

“…RPS‐30 UbL is a ubiquitin‐like protein and its homologue in human functions in various biological processes by covalently binding to various target proteins, such as pro‐apoptotic protein Bcl‐G, phagocytosis‐regulated protein endophilin II and invasion‐related protein IGF2BP2 18,19,41,42 . The structure of ‘beta folding grip’ and the internal lysine residues, K27 and K43 in RPS‐30 UbL might indicate its function in ubiquitin‐like modification and the formation of the poly‐ubiquitin chain.…”