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Defining the Program of Maternal mRNA Translation during In vitro Maturation using a Single Oocyte Reporter Assay
Published on: June 16, 2021
LSM14B is an Oocyte-Specific RNA-Binding Protein Indispensable for Maternal mRNA Metabolism and Oocyte Development in
Hui Li1,2, Hailian Zhao3, Chunhui Yang1
1Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, 266237, P. R. China.
Abstract:
Mammalian oogenesis features reliance on the mRNAs produced and stored during early growth phase. These are essential for producing an oocyte competent to undergo meiotic maturation and embryogenesis later when oocytes are transcriptionally silent. The fate of maternal mRNAs hence ensures the success of oogenesis and the quality of the resulting eggs. Nevertheless, how the fate of maternal mRNAs is determined remains largely elusive. RNA-binding proteins (RBPs) are crucial regulators of oogenesis, yet the identity of the full complement of RBPs expressed in oocytes is unknown. Here, a global view of oocyte-expressed RBPs is presented: mRNA-interactome capture identifies 1396 RBPs in mouse oocytes. An analysis of one of these RBPs, LSM family member 14 (LSM14B), demonstrates that this RBP is specific to oocytes and associated with many networks essential for oogenesis. Deletion of Lsm14b results in female-specific infertility and a phenotype characterized by oocytes incompetent to complete meiosis and early embryogenesis. LSM14B serves as an interaction hub for proteins and mRNAs throughout oocyte development and regulates translation of a subset of its bound mRNAs. Therefore, RNP complexes tethered by LSM14B are found exclusively in oocytes and are essential for the control of maternal mRNA fate and oocyte development.
Insights
Maternal mRNA fate is crucial for egg quality and oocyte development. This study identifies 1396 RNA-binding proteins (RBPs) in mouse oocytes, revealing LSM14B as essential for regulating mRNA translation and ensuring female fertility.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Developmental Biology
Background:
- Mammalian oogenesis relies on maternal mRNAs stored during early growth for later oocyte maturation and embryogenesis.
- The precise mechanisms governing maternal mRNA fate and the full repertoire of oocyte-expressed RNA-binding proteins (RBPs) remain largely unknown.
- RBPs are critical regulators of oogenesis, influencing mRNA stability, translation, and localization.
Purpose of the Study:
- To comprehensively identify RBPs expressed in mouse oocytes.
- To investigate the function of specific RBPs, particularly LSM14B, in oogenesis.
- To elucidate the role of RBPs in regulating maternal mRNA fate and oocyte developmental competence.
Main Methods:
- mRNA-interactome capture (IC) to globally identify RBPs in mouse oocytes.
- Bioinformatic analysis of identified RBPs and their associated networks.
- Generation and analysis of Lsm14b knockout mouse models to assess its in vivo function.
Main Results:
- Identification of 1396 RBPs in mouse oocytes, providing a global view of the oocyte RBP landscape.
- LSM14B was identified as an oocyte-specific RBP involved in essential oogenesis networks.
- Lsm14b deletion led to female-specific infertility, with oocytes unable to complete meiosis or support early embryogenesis, highlighting LSM14B's critical role.
Conclusions:
- LSM14B functions as a key interaction hub for proteins and mRNAs in oocytes.
- LSM14B regulates the translation of specific bound mRNAs, controlling maternal mRNA fate.
- Oocyte-specific RNP complexes mediated by LSM14B are indispensable for successful oocyte development and fertility.
