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oocytes, kiaa, kiaazpcko, pubmed, oocyte, rna, control, google, scholar, fig, supplementary, cas, cell, development, mice, srsf, analysis, mouse, exon, data, genes, cells, deletion, ythdc, events, follicles, follicular, nuclear, central, expression, factors, splicing, table, nature, alternative, mrna, ovaries, gene, experiments, weekold, independent, rnaseq, performed, follicle, modification, maturation, chromatin, competence, female, gvbd,

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supplementary table s3 supplementary table s4 supplementary table s5 supplementary table s6 supplementary table s7 figure legends supplementary table s1 listed supplementary table s2 supplementary table s2 nature portfolio permissions reprints c-abl/tap63-dependent oocyte death privacy policy national key research supplementary table animal research committee nature science foundation mettl3-mediated mrna n6-methyladenosine graded ethanol solutions ovarian research advertising serine/arginine-rich protein family gene tools oocyte library construction thermo fisher scientific opti-mem media nature n-terminal ha-tagged microrna-driven translational repression generate sequence libraries n6-methyladenosine sequencing highlights mrna n6-methyladenosine modifications full-length rna-seq thermo scientific c57bl/6n genomic background c57bl/6j genomic background paired-end 150-bp sequencing kiaa1429-mediated pre-mrna n6-methyladenosine-modified rna kiaa1429-mediated rna metabolism kiaa1429-mediated m6a modification full access social media n6-methyladenosine-dependent regulation integrating rna-seq data n6-methyladenosine binding protein oocyte-dependent activation replicate rna-seq data il-7/stat5/socs pathways full size image

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         headline:Oocyte competence is maintained by m6A methyltransferase KIAA1429-mediated RNA metabolism during mouse follicular development
         description:KIAA1429 (also known as vir-like m6A methyltransferase-associated protein (VIRMA)), a newly identified component of the RNA m6A methyltransferase complex, plays critical roles in guiding region-selective m6A deposition. However, in mammals, whether KIAA1429 mediates RNA m6A regulatory pathway functions in vivo remains unknown. Here, we show that the Kiaa1429-specific deficiency in oocytes resulted in female infertility with defective follicular development and fully grown germinal vesicle (GV) oocytes failing to undergo germinal vesicle breakdown (GVBD) and consequently losing the ability to resume meiosis. The oocyte growth is accompanied by the accumulation of abundant RNAs and posttranscriptional regulation. We found that the loss of Kiaa1429 could also lead to abnormal RNA metabolism in GV oocytes. RNA-seq profiling revealed that Kiaa1429 deletion altered the expression pattern of the oocyte-derived factors essential for follicular development. In addition, our data show that the conditional depletion of Kiaa1429 decreased the m6A levels in oocytes and mainly affected the alternative splicing of genes associated with oogenesis. In summary, the m6A methyltransferase KIAA1429-mediated RNA metabolism plays critical roles in folliculogenesis and the maintenance of oocyte competence.
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      description:KIAA1429 (also known as vir-like m6A methyltransferase-associated protein (VIRMA)), a newly identified component of the RNA m6A methyltransferase complex, plays critical roles in guiding region-selective m6A deposition. However, in mammals, whether KIAA1429 mediates RNA m6A regulatory pathway functions in vivo remains unknown. Here, we show that the Kiaa1429-specific deficiency in oocytes resulted in female infertility with defective follicular development and fully grown germinal vesicle (GV) oocytes failing to undergo germinal vesicle breakdown (GVBD) and consequently losing the ability to resume meiosis. The oocyte growth is accompanied by the accumulation of abundant RNAs and posttranscriptional regulation. We found that the loss of Kiaa1429 could also lead to abnormal RNA metabolism in GV oocytes. RNA-seq profiling revealed that Kiaa1429 deletion altered the expression pattern of the oocyte-derived factors essential for follicular development. In addition, our data show that the conditional depletion of Kiaa1429 decreased the m6A levels in oocytes and mainly affected the alternative splicing of genes associated with oogenesis. In summary, the m6A methyltransferase KIAA1429-mediated RNA metabolism plays critical roles in folliculogenesis and the maintenance of oocyte competence.
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            name:Nanjing Medical University
            address:
               name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Yuanlin He
      affiliation:
            name:Nanjing Medical University
            address:
               name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Yumeng Cao
      affiliation:
            name:Nanjing Medical University
            address:
               name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Qiqi Cao
      affiliation:
            name:Nanjing Medical University
            address:
               name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Qianneng Lu
      affiliation:
            name:Nanjing Medical University
            address:
               name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Shuai Zhou
      affiliation:
            name:Nanjing Medical University
            address:
               name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Lu Liu
      affiliation:
            name:Nanjing Medical University
            address:
               name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Li Liu
      affiliation:
            name:Nanjing Medical University
            address:
               name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Bin Shen
      url:http://orcid.org/0000-0002-8946-8448
      affiliation:
            name:Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Hospital, Nanjing Medical University
            address:
               name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Hospital, Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Wenjie Shu
      affiliation:
            name:Beijing Institute of Radiation Medicine
            address:
               name:Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Ran Huo
      affiliation:
            name:Nanjing Medical University
            address:
               name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
      name:Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, China
      name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
      name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Hospital, Nanjing Medical University, Nanjing, China
      name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
      name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
      name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
      name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
      name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
      name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
      name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
      name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
      name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Hospital, Nanjing Medical University, Nanjing, China
      name:Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, China
      name:State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China
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