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差异可变剪接图谱鉴定出哺乳动物早期胚胎发育中潜在具有功能的RNA结合蛋白。

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

作者信息

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

机构信息

State Key Laboratory of Reproduction Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu 210029, China.

Reproductive Medical Center of Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, China.

出版信息

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

DOI:10.1016/j.isci.2024.109104
PMID:38433915
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10904927/
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.

摘要

可变剪接（AS）作为重要的转录后调控机制之一，在胚胎发生过程中一直未得到充分研究。在本研究中，我们全面收集并分析了人类和小鼠早期胚胎的转录组数据。我们发现可变剪接在这一过程中发挥着重要作用，并预测了与生殖发育相关的候选RNA结合蛋白（RBP）调控因子。发现诸如EIF4A3、MAK16、SRSF2和UTP23等预测的RBP与生殖障碍有关。通过Smart-seq2测序分析，我们在Eif4a3基因敲低的胚胎中鉴定出5445个异常可变剪接事件。这些事件优先与RNA加工相关。总之，我们关于可变剪接事件的格局和潜在功能的研究工作将推动对调控哺乳动物早期胚胎发育的详细机制和关键因素的进一步研究，并促进针对这一关键生物学过程中疾病的药物治疗方法的启发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/b6a3d33c6e22/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/41959860d4ff/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/6d8964ba1a84/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/1d3a3f0f5261/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/a59cbc34d086/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/22bfca3173eb/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/2fdc3fe9e261/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/4a0a0444a14b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/b6a3d33c6e22/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/41959860d4ff/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/6d8964ba1a84/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/1d3a3f0f5261/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/a59cbc34d086/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/22bfca3173eb/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/2fdc3fe9e261/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/4a0a0444a14b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf3/10904927/b6a3d33c6e22/gr7.jpg

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