Requirement of the 3'-UTR-dependent suppression of DAZL in oocytes for pre-implantation mouse development
Functional oocytes are produced through complex molecular and cellular processes. In particular, the contribution of post-transcriptional gene regulation mediated by RNA-binding proteins (RBPs) is crucial for controlling proper gene expression during this process. DAZL (deleted in azoospermia-like)...
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Published in | PLoS genetics Vol. 14; no. 6; p. e1007436 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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Public Library of Science
08.06.2018
Public Library of Science (PLoS) |
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Abstract | Functional oocytes are produced through complex molecular and cellular processes. In particular, the contribution of post-transcriptional gene regulation mediated by RNA-binding proteins (RBPs) is crucial for controlling proper gene expression during this process. DAZL (deleted in azoospermia-like) is one of the RBPs required for the sexual differentiation of primordial germ cells and for the progression of meiosis in ovulated oocytes. However, the involvement of DAZL in the development of follicular oocytes is still unknown. Here, we show that Dazl is translationally suppressed in a 3'-UTR-dependent manner in follicular oocytes, and this suppression is required for normal pre-implantation development. We found that suppression of DAZL occurred in postnatal oocytes concomitant with the formation of primordial follicles, whereas Dazl mRNA was continuously expressed throughout oocyte development, raising the possibility that DAZL is dispensable for the survival and growth of follicular oocytes. Indeed, follicular oocyte-specific knockout of Dazl resulted in the production of normal number of pups. On the other hand, genetically modified female mice that overexpress DAZL produced fewer numbers of pups than the control due to defective pre-implantation development. Our data suggest that post-transcriptional suppression of DAZL in oocytes is an important mechanism controlling gene expression in the development of functional oocytes. |
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AbstractList | Functional oocytes are produced through complex molecular and cellular processes. In particular, the contribution of post-transcriptional gene regulation mediated by RNA-binding proteins (RBPs) is crucial for controlling proper gene expression during this process. DAZL (deleted in azoospermia-like) is one of the RBPs required for the sexual differentiation of primordial germ cells and for the progression of meiosis in ovulated oocytes. However, the involvement of DAZL in the development of follicular oocytes is still unknown. Here, we show that Dazl is translationally suppressed in a 3′-UTR-dependent manner in follicular oocytes, and this suppression is required for normal pre-implantation development. We found that suppression of DAZL occurred in postnatal oocytes concomitant with the formation of primordial follicles, whereas Dazl mRNA was continuously expressed throughout oocyte development, raising the possibility that DAZL is dispensable for the survival and growth of follicular oocytes. Indeed, follicular oocyte-specific knockout of Dazl resulted in the production of normal number of pups. On the other hand, genetically modified female mice that overexpress DAZL produced fewer numbers of pups than the control due to defective pre-implantation development. Our data suggest that post-transcriptional suppression of DAZL in oocytes is an important mechanism controlling gene expression in the development of functional oocytes. Functional oocytes are produced through complex molecular and cellular processes. In particular, the contribution of post-transcriptional gene regulation mediated by RNA-binding proteins (RBPs) is crucial for controlling proper gene expression during this process. DAZL (deleted in azoospermia-like) is one of the RBPs required for the sexual differentiation of primordial germ cells and for the progression of meiosis in ovulated oocytes. However, the involvement of DAZL in the development of follicular oocytes is still unknown. Here, we show that Dazl is translationally suppressed in a 3′-UTR-dependent manner in follicular oocytes, and this suppression is required for normal pre-implantation development. We found that suppression of DAZL occurred in postnatal oocytes concomitant with the formation of primordial follicles, whereas Dazl mRNA was continuously expressed throughout oocyte development, raising the possibility that DAZL is dispensable for the survival and growth of follicular oocytes. Indeed, follicular oocyte-specific knockout of Dazl resulted in the production of normal number of pups. On the other hand, genetically modified female mice that overexpress DAZL produced fewer numbers of pups than the control due to defective pre-implantation development. Our data suggest that post-transcriptional suppression of DAZL in oocytes is an important mechanism controlling gene expression in the development of functional oocytes. Evolutionarily conserved DAZ family genes are indispensably involved in germline development. Dazl ( deleted in azoospermia-like ) is a member of the mammalian DAZ family of genes, and plays crucial roles in the sexual differentiation of primordial germ cells and spermatogenesis, and is implicated in the progression of meiosis II in ovulated eggs. Despite its importance for multiple processes during germline development, its participation in follicular oocyte development is enigmatic. This study addressed this issue and found that DAZL is translationally suppressed in postnatal oocytes in a 3′-UTR-dependent manner. Furthermore, this suppression is required for normal pre-implantation development after fertilization, suggesting the presence of an unidentified mechanism controlling DAZL expression. Our data provide new insights for post-transcriptional gene regulation involved in oocyte development. |
Audience | Academic |
Author | Saga, Yumiko Suzuki, Atsushi Fukuda, Kurumi Naka, Takuma Kato, Yuzuru Masuda, Aki |
AuthorAffiliation | 4 Department of Biological Science, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan 2 Department of Genetics, SOKENDAI, Mishima, Shizuoka, Japan 1 Division of Mammalian Development, Genetic Strains Research Center, National Institute of Genetics, Mishima, Shizuoka, Japan 3 Division of Materials Science and Chemical Engineering, Graduate School of Engineering, Faculty of Engineering, Yokohama National University, Yokohama Kanagawa, Japan University of Pennsylvania, UNITED STATES |
AuthorAffiliation_xml | – name: 4 Department of Biological Science, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan – name: University of Pennsylvania, UNITED STATES – name: 1 Division of Mammalian Development, Genetic Strains Research Center, National Institute of Genetics, Mishima, Shizuoka, Japan – name: 3 Division of Materials Science and Chemical Engineering, Graduate School of Engineering, Faculty of Engineering, Yokohama National University, Yokohama Kanagawa, Japan – name: 2 Department of Genetics, SOKENDAI, Mishima, Shizuoka, Japan |
Author_xml | – sequence: 1 givenname: Kurumi surname: Fukuda fullname: Fukuda, Kurumi organization: Department of Genetics, SOKENDAI, Mishima, Shizuoka, Japan – sequence: 2 givenname: Aki surname: Masuda fullname: Masuda, Aki organization: Division of Mammalian Development, Genetic Strains Research Center, National Institute of Genetics, Mishima, Shizuoka, Japan – sequence: 3 givenname: Takuma surname: Naka fullname: Naka, Takuma organization: Division of Materials Science and Chemical Engineering, Graduate School of Engineering, Faculty of Engineering, Yokohama National University, Yokohama Kanagawa, Japan – sequence: 4 givenname: Atsushi orcidid: 0000-0002-8413-6436 surname: Suzuki fullname: Suzuki, Atsushi organization: Division of Materials Science and Chemical Engineering, Graduate School of Engineering, Faculty of Engineering, Yokohama National University, Yokohama Kanagawa, Japan – sequence: 5 givenname: Yuzuru orcidid: 0000-0002-4001-3792 surname: Kato fullname: Kato, Yuzuru organization: Department of Genetics, SOKENDAI, Mishima, Shizuoka, Japan – sequence: 6 givenname: Yumiko surname: Saga fullname: Saga, Yumiko organization: Department of Biological Science, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan |
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CitedBy_id | crossref_primary_10_1038_s41586_023_06228_9 crossref_primary_10_1093_hmg_ddae077 crossref_primary_10_1096_fj_202101585R crossref_primary_10_1002_advs_202205500 crossref_primary_10_1242_dev_187773 crossref_primary_10_1096_fj_201901247R crossref_primary_10_1016_j_isci_2021_102890 crossref_primary_10_1242_dev_161471 crossref_primary_10_1093_nsr_nwy163 crossref_primary_10_15252_embr_201948251 crossref_primary_10_1111_brv_12937 crossref_primary_10_1039_C9FO01485C crossref_primary_10_1038_s41467_020_15209_9 |
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SubjectTerms | 3' Untranslated regions 3' Untranslated Regions - genetics Animals Binding proteins Biology and Life Sciences Chemical engineering Embryonic Development - genetics Engineering schools Female Females Follicles Funding Gene expression Gene Expression Regulation, Developmental Gene regulation Genetic aspects Genetic regulation Genetic research Genetics Genomes Germ cells Investigations Materials science Medicine and Health Sciences Meiosis Mice Mice, Inbred C57BL Mice, Knockout Oocytes Oocytes - growth & development Oocytes - metabolism Oogenesis - genetics Ovarian Follicle - cytology Ovarian Follicle - growth & development Ovarian Follicle - metabolism Post-transcription Proteins Research and Analysis Methods RNA, Messenger - genetics RNA-binding protein RNA-Binding Proteins - genetics Sex differentiation Supervision |
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Title | Requirement of the 3'-UTR-dependent suppression of DAZL in oocytes for pre-implantation mouse development |
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