Recently, "LSM14B is an Oocyte-Specific RNA-Binding Protein Indispensable for Maternal mRNA Metabolism and Oocyte Development in Mice" was published in Advanced Science by a research group led by Prof. Su Youqiang from the School of Life Sciences and Prof. Xue Yuchao from the Institute of Biophysics, Chinese Academy of Sciences. Li Hui, postdoctoral fellow of the School of Life Sciences, and Zhao Hailian, PhD student of the Institute of Biophysics of the Chinese Academy of Sciences are co-first authors. Prof. Su Youqiang and Prof. Xue Yuchao are co-corresponding authors. Shandong University is the first author and corresponding author institute.

The development and maturation of oocytes are determined by their own unique gene expression programs and regulatory mechanisms. In most mammals, the gene transcription activity of oocytes occurs in their early growth stage and stops at the end of their growth, making the subsequent oocyte maturation, fertilization and early embryonic development completely dependent on the mRNA expressed and stored during growth. Therefore, the metabolic regulation of post-transcriptional mRNA becomes the key mode of gene expression regulation in oocytes, while the effective storage of maternal mRNA and its selective translation and degradation at specific developmental and mature nodes (collectively referred to as the fate of maternal mRNA) become the key factors that restrict the success or failure of oogenesis and the quality of oocytes. However, the specific molecular mechanism that determines the fate of maternal mRNA is unclear, which is the hot spot and frontier in the field of oogenesis.

RNA binding protein (RBP) plays an important role in the regulation of maternal mRNA metabolism and oogenesis, but the specific mechanism has not been clarified. In this study, RNA-Interactome Capture (RIC) was used to isolate and identify the RBPome of mouse oocytes for the first time. It was also found that LSM14B, which was highly conserved in evolution, was the core RBP specifically expressed by oocytes and essential for oocyte maturation and regulation of maternal mRNA metabolism. The absence of LSM14B did not affect male reproduction, but female mice became infertile because their oocytes entered the interphase after completing the first meiosis. By isolation and identification of mRNA and protein bound by LSM14B, this study revealed that LSM14B, as the core organizer, formed a dynamic multifunctional ribonucleoprotein (RNP) complex with proteins and mRNA that were essential for oogenesis to regulate the metabolism of maternal mRNA and oocyte development and maturation. These factors included BRWD1, CKS2, DNMT1, DPPA3, GDF9, GPR3, MARF1, MOS, NLRP5, NOBOX, NPM2, PADI6, PDE3A, TRIM28 and UHRF1. In addition, LSM14B bound to multiple RBPS involved in different mRNA metabolic processes (such as CNOT1, CPEB1, CPSF1, DDX6, EDC4, EIF4E1B, EIF4ENIF1, ESRP1, MARF1, PABPC1L, PATL2, YBX2, and ZAR1) and regulated oocyte translation. At the same time, in view of the genetic mutation of some RBPs (such as PATL2 and EIF4ENIF1) leading to human oocyte maturation defects or premature ovarian failure, this study also has important guiding significance for the diagnosis and treatment of infertility caused by genetic defects or the decline of egg quality caused by ageing.

The research was supported by the National Major Scientific Research Program and the Natural Science Foundation of China, the major basic research project of the Natural Science Foundation of Shandong Province, and the "double first-class" discipline construction project of Shandong University.

Link to the paper: https://doi.org/10.1002/advs.202300043