Alternative splicing of CARM1 regulated by LincGET-guided paraspeckles biases the first cell fate in mammalian early embryos.

Autor: Wang J; College of Life Science, Northeast Agricultural University, Harbin, China. wangjiaqiang@neau.edu.cn., Zhang Y; College of Life Science, Northeast Agricultural University, Harbin, China., Gao J; College of Life Science, Northeast Agricultural University, Harbin, China., Feng G; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China., Liu C; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China., Li X; College of Life Science, Northeast Agricultural University, Harbin, China.; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China., Li P; College of Life Science, Northeast Agricultural University, Harbin, China.; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China., Liu Z; College of Life Science, Northeast Agricultural University, Harbin, China., Lu F; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.; University of Chinese Academy of Sciences, Beijing, China., Wang L; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. wangleyun0828@hotmail.com., Li W; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. liwei@ioz.ac.cn.; University of Chinese Academy of Sciences, Beijing, China. liwei@ioz.ac.cn.; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. liwei@ioz.ac.cn., Zhou Q; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. qzhou@ioz.ac.cn.; University of Chinese Academy of Sciences, Beijing, China. qzhou@ioz.ac.cn.; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. qzhou@ioz.ac.cn., Liu Y; College of Life Science, Northeast Forestry University, Harbin, China. liuys1126@foxmail.com.
Jazyk: angličtina
Zdroj: Nature structural & molecular biology [Nat Struct Mol Biol] 2024 Sep; Vol. 31 (9), pp. 1341-1354. Date of Electronic Publication: 2024 Apr 24.
DOI: 10.1038/s41594-024-01292-9
Abstrakt: The heterogeneity of CARM1 controls first cell fate bias during early mouse development. However, how this heterogeneity is established is unknown. Here, we show that Carm1 mRNA is of a variety of specific exon-skipping splicing (ESS) isoforms in mouse two-cell to four-cell embryos that contribute to CARM1 heterogeneity. Disruption of paraspeckles promotes the ESS of Carm1 precursor mRNAs (pre-mRNAs). LincGET, but not Neat1, is required for paraspeckle assembly and inhibits the ESS of Carm1 pre-mRNAs in mouse two-cell to four-cell embryos. We further find that LincGET recruits paraspeckles to the Carm1 gene locus through HNRNPU. Interestingly, PCBP1 binds the Carm1 pre-mRNAs and promotes its ESS in the absence of LincGET. Finally, we find that the ESS seen in mouse two-cell to four-cell embryos decreases CARM1 protein levels and leads to trophectoderm fate bias. Our findings demonstrate that alternative splicing of CARM1 has an important role in first cell fate determination.
(© 2024. The Author(s).)
Databáze: MEDLINE
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