LSM1-mediated Major Satellite RNA decay is required for nonequilibrium histone H3.3 incorporation into parental pronuclei

Jiang Zhu; Kang Chen; Yu H Sun; Wen Ye; Juntao Liu; Dandan Zhang; Nan Su; Li Wu; Xiaochen Kou; Yanhong Zhao; Hong Wang; Shaorong Gao; Lan Kang

doi:10.1038/s41467-023-36584-z

LSM1-mediated Major Satellite RNA decay is required for nonequilibrium histone H3.3 incorporation into parental pronuclei

Nat Commun. 2023 Feb 21;14(1):957. doi: 10.1038/s41467-023-36584-z.

Authors

Jiang Zhu^#^{1

2}, Kang Chen^#^{1

3

4}, Yu H Sun^#⁵, Wen Ye¹, Juntao Liu¹, Dandan Zhang¹, Nan Su¹, Li Wu⁶, Xiaochen Kou², Yanhong Zhao², Hong Wang⁶, Shaorong Gao^{7

8

9}, Lan Kang^{10

11}

Affiliations

¹ Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, 200120, Shanghai, China.
² Frontier Science Center for Stem Cell Research, Tongji University, 200092, Shanghai, China.
³ Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China.
⁴ University of Chinese Academy of Sciences, 100049, Beijing, China.
⁵ Departments of Biology, University of Rochester, 14642, Rochester, NY, USA.
⁶ Clinical and Translation Research Center of Shanghai First Maternity & Infant Hospital, School of Life Sciences and Technology, Tongji University, 200092, Shanghai, China.
⁷ Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, 200120, Shanghai, China. gaoshaorong@tongji.edu.cn.
⁸ Frontier Science Center for Stem Cell Research, Tongji University, 200092, Shanghai, China. gaoshaorong@tongji.edu.cn.
⁹ Clinical and Translation Research Center of Shanghai First Maternity & Infant Hospital, School of Life Sciences and Technology, Tongji University, 200092, Shanghai, China. gaoshaorong@tongji.edu.cn.
¹⁰ Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, 200120, Shanghai, China. kanglan@tongji.edu.cn.
¹¹ Frontier Science Center for Stem Cell Research, Tongji University, 200092, Shanghai, China. kanglan@tongji.edu.cn.

^# Contributed equally.

Abstract

Epigenetic reprogramming of the parental genome is essential for zygotic genome activation and subsequent embryo development in mammals. Asymmetric incorporation of histone H3 variants into the parental genome has been observed previously, but the underlying mechanism remains elusive. In this study, we discover that RNA-binding protein LSM1-mediated major satellite RNA decay plays a central role in the preferential incorporation of histone variant H3.3 into the male pronucleus. Knockdown of Lsm1 disrupts nonequilibrium pronucleus histone incorporation and asymmetric H3K9me3 modification. Subsequently, we find that LSM1 mainly targets major satellite repeat RNA (MajSat RNA) for decay and that accumulated MajSat RNA in Lsm1-depleted oocytes leads to abnormal incorporation of H3.1 into the male pronucleus. Knockdown of MajSat RNA reverses the anomalous histone incorporation and modifications in Lsm1-knockdown zygotes. Our study therefore reveals that accurate histone variant incorporation and incidental modifications in parental pronuclei are specified by LSM1-dependent pericentromeric RNA decay.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Nucleus* / metabolism
Embryonic Development / genetics
Histones* / metabolism
Male
Mammals / genetics
RNA / metabolism
RNA Stability
Zygote / metabolism

Substances

Histones
RNA