Differential alternative splicing landscape identifies potentially functional RNA binding proteins in early embryonic development in mammals

Jianhua Chen; Yanni He; Liangliang Chen; Tian Wu; Guangping Yang; Hui Luo; Saifei Hu; Siyue Yin; Yun Qian; Hui Miao; Na Li; Congxiu Miao; Ruizhi Feng

doi:10.1016/j.isci.2024.109104

Differential alternative splicing landscape identifies potentially functional RNA binding proteins in early embryonic development in mammals

iScience. 2024 Feb 2;27(3):109104. doi: 10.1016/j.isci.2024.109104. eCollection 2024 Mar 15.

Authors

Jianhua Chen¹, Yanni He¹, Liangliang Chen¹, Tian Wu¹, Guangping Yang¹, Hui Luo¹, Saifei Hu¹, Siyue Yin¹, Yun Qian², Hui Miao³, Na Li³, Congxiu Miao³, Ruizhi Feng^{1

2}

Affiliations

¹ State Key Laboratory of Reproduction Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
² Reproductive Medical Center of Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, China.
³ Department of Reproductive Genetics, Heping Hospital of Changzhi Medical College, Key Laboratory of Reproduction Engineer of Shanxi Health Committee, Changzhi, Shanxi 046000, China.

Abstract

Alternative splicing (AS) as one of the important post-transcriptional regulatory mechanisms has been poorly studied during embryogenesis. In this study, we comprehensively collected and analyzed the transcriptome data of early embryos from human and mouse. We found that AS plays an important role in this process and predicted candidate RNA binding protein (RBP) regulators that are associated with reproductive development. The predicted RBPs such as EIF4A3, MAK16, SRSF2, and UTP23 were found to be associated with reproductive disorders. By Smart-seq2 sequencing analysis, we identified 5445 aberrant alternative splicing events in Eif4a3-knockdown embryos. These events were preferentially associated with RNA processing. In conclusion, our work on the landscape and potential function of alternative splicing events will boost further investigation of detailed mechanisms and key factors regulating mammalian early embryo development and promote the inspiration of pharmaceutical approaches for disorders in this crucial biology process.

Keywords: Embryology; Molecular biology; Systems biology.