Ran‑binding protein 3 is associated with human spermatogenesis and male infertility

Tang, Wenhao; Zhu, Yutian; Qin, Weibing; Zhang, Haitao; Zhang, Hongliang; Lin, Haocheng; Zhang, Xiumei; Zhuang, Xincun; Tang, Yunge; Hui, Jian

doi:10.1111/and.13446

Cited by 6 publications

(3 citation statements)

References 32 publications

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“…RANBP3 is a relatively unknown protein with connections to RNA and protein nucleo-transport ( Boudhraa et al, 2020 ). Unfortunately, it is not known if RANBP3 depletion results in a loss of fertility although one study has found an association between decreased RANBP3 expression and human infertility ( Tang et al, 2020 ). We investigated the localization of RANBP3 in meiotic spreads and found that in cells derived from wild-type or vehicle-treated mice, RANBP3 localizes to the sex body at pachynema ( Figure 4E and F , Figure 4—figure supplement 2A and B ).…”

Section: Resultsmentioning

confidence: 99%

Phosphoproteomics of ATR signaling in mouse testes

Sims

Faça

Pereira

et al. 2022

eLife

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The phosphatidylinositol 3′ kinase (PI3K)‐related kinase ATR is crucial for mammalian meiosis. ATR promotes meiotic progression by coordinating key events in DNA repair, meiotic sex chromosome inactivation (MSCI), and checkpoint-dependent quality control during meiotic prophase I. Despite its central roles in meiosis, the ATR-dependent meiotic signaling network remains largely unknown. Here, we used phosphoproteomics to define ATR signaling events in testes from mice following chemical and genetic ablation of ATR signaling. Quantitative analysis of phosphoproteomes obtained after germ cell-specific genetic ablation of the ATR activating 9-1-1 complex or treatment with ATR inhibitor identified over 14,000 phosphorylation sites from testes samples, of which 401 phosphorylation sites were found to be dependent on both the 9-1-1 complex and ATR. Our analyses identified ATR-dependent phosphorylation events in crucial DNA damage signaling and DNA repair proteins including TOPBP1, SMC3, MDC1, RAD50, and SLX4. Importantly, we identified ATR and RAD1-dependent phosphorylation events in proteins involved in mRNA regulatory processes, including SETX and RANBP3, whose localization to the sex body was lost upon ATR inhibition. In addition to identifying the expected ATR-targeted S/T-Q motif, we identified enrichment of an S/T-P-X-K motif in the set of ATR-dependent events, suggesting that ATR promotes signaling via proline-directed kinase(s) during meiosis. Indeed, we found that ATR signaling is important for the proper localization of CDK2 in spermatocytes. Overall, our analysis establishes a map of ATR signaling in mouse testes and highlights potential meiotic-specific actions of ATR during prophase I progression.

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Section: Resultsmentioning

confidence: 99%

Phosphoproteomics of ATR signaling in mouse testes

Sims

Faça

Pereira

et al. 2022

eLife

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“…Moreover, cfDNA from breast cancer patients exhibited a methylation pattern of these three genes that mirrored that of cancer tissue. The RAN-binding protein 3 (RANBP3) gene, situated on chromosome 19, has been predominantly associated with the proliferation of leukaemia cells (30) and male sperm production (31), with limited studies exploring its connection to breast cancer. Notably, the anthracycline drug doxorubicin (Dox), a primary treatment for breast tumours and adjuvant therapy drug, induces significant toxicity to the myocardium while eliminating cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Value of altered methylation patterns of genes RANBP3, LCP2 and GRAP2 in cfDNA in breast cancer diagnosis

Hu,

Mao,

Lan

et al. 2024

J Med Biochemistry

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Background: The purpose of this study was to investigate the potential of plasma cfDNA methylation patterns in reflecting tumor methylation changes, focusing on three candidate sites, cg02469161, cg11528914, and cg20131654. These sites were selected for verification, with a particular emphasis on their association with breast cancer. Methods: We conducted a comprehensive analysis of 850k whole-methylation sequencing data to identify potential markers for breast cancer detection. Subsequently, we examined the methylation status of genes RANBP3, LCP2, and GRAP2, where the aforementioned sites are located, using cancer and cancer-adjacent tissues from 17 breast cancer patients. We also assessed the methylation patterns in different molecular subtypes and pathological grades of breast cancer. Additionally, we compared the methylation levels of these genes in plasma cfDNA to their performance in tissues. Results: Our analysis revealed that RANBP3, LCP2, and GRAP2 genes exhibited significant methylation differences between cancer and cancer-adjacent tissues. In breast cancer, these genes displayed diagnostic efficiencies of 91.0%, 90.6%, and 92.2%, respectively. Notably, RANBP3 showed a tendency towards lower methylation in HR+ breast cancer, and LCP2 methylation was correlated with tumor malignancy. Importantly, the methylation levels of these three genes in plasma cfDNA closely mirrored their tissue counterparts, with diagnostic efficiencies of 83.3%, 83.9%, and 77.6% for RANBP3, LCP2, and GRAP2, respectively. Conclusions: Our findings suggest that RANBP3, LCP2, and GRAP2 genes, located at the identified methylation sites, can serve as valuable blood molecular markers for the auxiliary diagnosis of breast cancer. This research provides a foundation for further exploration of gene methylation pattern changes in cfDNA for the detection of breast cancer and other cancer types.

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“…Each phase is strictly regulated by transcriptional factors, hormones, epigenetic regulators, and lncRNAs. Disruption of any steps of spermatogenesis, referred to as maturation arrest (MA), causes male infertility [ 77 ]. Nonobstructive azoospermia (NOA) is considered the most severe case of male infertility, and it is characterized as no sperm in the ejaculate due to failure of spermatogenesis [ 78 ].…”

Section: Lncrnas In Reproductive Diseasesmentioning

confidence: 99%

Long Noncoding RNA Mediated Regulation in Human Embryogenesis, Pluripotency, and Reproduction

Liu

Fang

2022

Stem Cells International

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Long noncoding RNAs (lncRNAs), a class of noncoding RNAs with more than 200 bp in length, are produced by pervasive transcription in mammalian genomes and regulate gene expression through various action mechanisms. Accumulating data indicate that lncRNAs mediate essential biological functions in human development, including early embryogenesis, induction of pluripotency, and germ cell development. Comprehensive analysis of sequencing data highlights that lncRNAs are expressed in a stage-specific and human/primate-specific pattern during early human development. They contribute to cell fate determination through interacting with almost all classes of cellular biomolecules, including proteins, DNA, mRNAs, and microRNAs. Furthermore, the expression of a few of lncRNAs is highly associated with the pathogenesis and progression of many reproductive diseases, suggesting that they could serve as candidate biomarkers for diagnosis or novel targets for treatment. Here, we review research on lncRNAs and their roles in embryogenesis, pluripotency, and reproduction. We aim to identify the underlying molecular mechanisms essential for human development and provide novel insight into the causes and treatments of human reproductive diseases.

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Ran‑binding protein 3 is associated with human spermatogenesis and male infertility

Cited by 6 publications

References 32 publications

Phosphoproteomics of ATR signaling in mouse testes

Phosphoproteomics of ATR signaling in mouse testes

Value of altered methylation patterns of genes RANBP3, LCP2 and GRAP2 in cfDNA in breast cancer diagnosis

Long Noncoding RNA Mediated Regulation in Human Embryogenesis, Pluripotency, and Reproduction

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