دورية
Alternative splicing of CARM1 regulated by LincGET-guided paraspeckles biases the first cell fate in mammalian early embryos
| العنوان: | Alternative splicing of CARM1 regulated by LincGET-guided paraspeckles biases the first cell fate in mammalian early embryos |
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| المؤلفون: | Wang, Jiaqiang, Zhang, Yiwei, Gao, Jiaze, Feng, Guihai, Liu, Chao, Li, Xueke, Li, Pengcheng, Liu, Zhonghua, Lu, Falong, Wang, Leyun, Li, Wei, Zhou, Qi, Liu, Yusheng |
| المصدر: | Nature Structural and Molecular Biology; 20240101, Issue: Preprints p1-14, 14p |
| مستخلص: | 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 Carm1mRNA 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 Carm1precursor mRNAs (pre-mRNAs). LincGET, but not Neat1, is required for paraspeckle assembly and inhibits the ESS of Carm1pre-mRNAs in mouse two-cell to four-cell embryos. We further find that LincGETrecruits paraspeckles to the Carm1gene locus through HNRNPU. Interestingly, PCBP1 binds the Carm1pre-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. |
| قاعدة البيانات: | Supplemental Index |
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Full Text Finder | تدمد: | 15459993 15459985 |
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| DOI: | 10.1038/s41594-024-01292-9 |