LSM14B is essential for oocyte meiotic maturation by regulating maternal mRNA storage and clearance

Author:

Wan Yanling1234,Yang Shuang5,Li Tongtong1234,Cai Yuling1234,Wu Xinyue1234,Zhang Mingyu1234,Muhammad Tahir123467,Huang Tao12348,Lv Yue89,Chan Wai-Yee1248,Lu Gang1248,Li Jingxin5ORCID,Sha Qian-Qian10ORCID,Chen Zi-Jiang1923481112ORCID,Liu Hongbin1234811ORCID

Affiliation:

1. Center for Reproductive Medicine, Shandong University , Jinan , Shandong  250012 , China

2. Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University , Jinan , Shandong  250012 , China

3. Shandong Provincial Clinical Medicine Research Center for Reproductive Health , Jinan , Shandong  250012 , China

4. State Key Laboratory of Reproductive Medicine and Offspring Health , Jinan , Shandong  250012 , China

5. Department of Physiology School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University , Jinan , Shandong 250012 , China

6. Department of Cell Biology and Anatomy , NY Medical College, 15 Dana Road , Valhalla, NY 10595 , USA

7. Institute of Molecular Biology and Biotechnology, The University of Lahore , Lahore 54000, Pakistan

8. CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, the Chinese University of Hong Kong , Hong Kong 999077, China

9. Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University , Jinan , Shandong 250012 , China

10. Fertility Preservation Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital , Guangzhou, Guangdong  510317 , China

11. Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences , Jinan, Shandong 250012,  China

12. Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics , Shanghai  200135 , China

Abstract

Abstract Fully grown oocytes remain transcriptionally quiescent, yet many maternal mRNAs are synthesized and retained in growing oocytes. We now know that maternal mRNAs are stored in a structure called the mitochondria-associated ribonucleoprotein domain (MARDO). However, the components and functions of MARDO remain elusive. Here, we found that LSM14B knockout prevents the proper storage and timely clearance of mRNAs (including Cyclin B1, Btg4 and other mRNAs that are translationally activated during meiotic maturation), specifically by disrupting MARDO assembly during oocyte growth and meiotic maturation. With decreased levels of storage and clearance, the LSM14B knockout oocytes failed to enter meiosis II, ultimately resulting in female infertility. Our results demonstrate the function of LSM14B in MARDO assembly, and couple the MARDO with mRNA clearance and oocyte meiotic maturation.

Funder

National Key Research and Development Program of China

Basic Science Center Program of the NFSC

Academic Promotion Programme of Shandong First Medical University

National Natural Science Foundation of China

Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences

Research Grants Council of Hong Kong

Shandong Provincial Key Research and Development Program

CUHK-SDU Joint Laboratory on Reproductive Genetics of CUHK

Major Innovation Projects in Shandong Province

Science Foundation for Distinguished Yong Scholars of Shandong

Taishan Scholars Program for Young Experts of Shandong Province

Publisher

Oxford University Press (OUP)

Subject

Genetics

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