According to incomplete statistics, there are about 15-20% of infertile couples worldwide, of which nearly 50% are caused by male factors. Environmental pollution, living pressure, genetic diseases and other factors are important reasons for male infertility, but currently more than half of infertile men are unable to determine the cause. Research Center of Excellence in Molecular Cell Sciences, Chinese Academy of Sciences The production regulatory “machine” activates the translation of proteins in mouse sperm cells and guarantees the production of functional sperm. This study revealed a new regulatory mechanism for translation and protein synthesis in sperm cells, and provided theoretical basis and methods for the diagnosis and treatment of sperm formation disorders and related male infertility. The results were published in the early morning of December 13, Beijing time in the international top academic journal Cell.
During the evolution of sperm cells into sperm, as the sperm deforms and the nucleus is compressed, the gene transcription activity in the nucleus will be completely stopped after a certain development stage, and those genes required for the later sperm cell development need to be transcribed into The messenger ribonucleic acid (mRNA) is then stored in the sperm cells in an inhibited state until it is activated for translation at a specific developmental stage and the synthetic protein plays a role. This is the classic “transcription-translation uncoupling” phenomenon during spermatogenesis, but how to make the “downtime” mRNA enter the “warehouse” to restart the working state? This has always been a mystery in reproductive biology, and scientists this time found the key “key” to open the door to the “warehouse”.
The research group of Liu Mofang and several laboratories have collaborated to find that a class of animal germ cell-specific small molecule non-coding RNA, piRNA, is formed by a PIWI / piRNA complex “machine” formed with the same germ cell-specific PIWI family proteins. “Forward” regulates the “reconstruction” of mRNA in sperm cells, and further identified the eukaryotic translation initiation factor eIF3f and the RNA-binding protein HuR to “assistance” to complete this process; by means of the HuR recognition “tag” on the mRNA, PIWI / piRNA can accurately select the target mRNA in the “mRNA warehouse”, and synergize with eIF3f, which is a key “key” to start translation, which is located around the “mRNA warehouse”, and initiates target mRNA translation and protein product generation, thereby ensuring sperm health development. If this process fails, mRNA will not be activated in time to make proteins, resulting in impeded sperm cell development and abnormal male reproduction. This study found an important mechanism of protein translation activation during sperm development, which greatly promoted our understanding and understanding of the biological process of sperm formation, and will provide theoretical basis and early molecular diagnosis and clinical treatment for related male infertility. Method strategy.
The research work was completed by Liu Mofang’s research group of Molecular Cell Center, Zhou Yu’s research group of Wuhan University, and Shi Huijuan’s research group of Shanghai Family Planning Research Institute. Dr. Peng Dai and Dr. Xin Wang from the Center for Molecular Cells, Dr. Lantao Gou from the University of California, San Diego, Li Zhitong, PhD student from the Center for Molecular Cells, Wen Ze, and Chen Zonggui, PhD student from Wuhan University, are the co-first authors of the research paper. This research was also supported by Professor Fu Xiangdong of the University of California, San Diego, Researcher Li Dangsheng of the Center for Molecular Cells, and Researcher Li Jinsong. This achievement was supported by the National Natural Science Foundation of China, the Ministry of Science and Technology, the Chinese Academy of Sciences, the Ministry of Education, the Shanghai Municipal Science and Technology Commission, the China Postdoctoral Foundation, SA-SIBS, etc. The data collection of this work was also supported by the Molecular and Cell Center Public Technology Service Center Animal Experiment Technology Platform, Molecular Biology Technology Platform and Cell Analysis Technology Platform, and the Protein Science Center of the Chinese Academy of Sciences