RNase H1 facilitates recombinase recruitment by degrading DNA–RNA hybrids during meiosis

Author:

Liu Chao12,Wang Liying1,Li Yanan3ORCID,Guo Mengmeng24,Hu Jun5,Wang Teng3,Li Mengjing6,Yang Zhuo7,Lin Ruoyao5,Xu Wei7ORCID,Chen Yinghong24,Luo Mengcheng8ORCID,Gao Fei24ORCID,Chen Jia-Yu5,Sun Qianwen79ORCID,Liu Hongbin6ORCID,Sun Bo3ORCID,Li Wei124ORCID

Affiliation:

1. Guangzhou Women and Children's Medical Center, Guangzhou Medical University , Guangzhou  510623, China

2. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Stem Cell and Regenerative Medicine Innovation Institute, Chinese Academy of Sciences , Beijing  100101, China

3. School of Life Science and Technology, ShanghaiTech University , Shanghai  201210, China

4. University of Chinese Academy of Sciences , Beijing  100049, China

5. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University , Nanjing  210023, China

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

7. Center for Plant Biology, School of Life Sciences, Tsinghua University , Beijing  100084, China

8. Department of Tissue and Embryology, School of Basic Medical Sciences, Wuhan University, Hubei Provincial Key Laboratory of Developmentally Originated Disease , Wuhan  430072, China

9. Tsinghua-Peking Center for Life Sciences , Beijing  100084, China

Abstract

Abstract DNA–RNA hybrids play various roles in many physiological progresses, but how this chromatin structure is dynamically regulated during spermatogenesis remains largely unknown. Here, we show that germ cell-specific knockout of Rnaseh1, a specialized enzyme that degrades the RNA within DNA–RNA hybrids, impairs spermatogenesis and causes male infertility. Notably, Rnaseh1 knockout results in incomplete DNA repair and meiotic prophase I arrest. These defects arise from the altered RAD51 and DMC1 recruitment in zygotene spermatocytes. Furthermore, single-molecule experiments show that RNase H1 promotes recombinase recruitment to DNA by degrading RNA within DNA–RNA hybrids and allows nucleoprotein filaments formation. Overall, we uncover a function of RNase H1 in meiotic recombination, during which it processes DNA–RNA hybrids and facilitates recombinase recruitment.

Funder

National Natural Science Foundation of China

National Science Fund for Distinguished Young Scholars

Natural Science Foundation of Shanghai

National Key Research and Development Program of China

Science and Technology Project of Guangzhou

Youth Talent Support Programme of Guangdong Provincial Association for Science and Technology

Publisher

Oxford University Press (OUP)

Subject

Genetics

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