School of Energy and Environment and State Key Laboratory of Marine Pollution, City University of Hong Kong, Kowloon, Hong Kong, China; Research Centre for the Oceans and Human Health, City University of Hong Kong Shenzhen Research Institute, Shenzhen 518057, China.
School of Energy and Environment and State Key Laboratory of Marine Pollution, City University of Hong Kong, Kowloon, Hong Kong, China; Research Centre for the Oceans and Human Health, City University of Hong Kong Shenzhen Research Institute, Shenzhen 518057, China.
J Mol Biol. 2022 Nov 15;434(21):167821. doi: 10.1016/j.jmb.2022.167821. Epub 2022 Sep 8.
Many vertebrate genes generate multiple transcript variants that may encode functionally distinct protein isoforms, but the transcriptomes of various developmental stages are poorly defined. Identifying the transcriptome and its regulation during the normal developmental process is the key to deciphering the developmental stage-specific functions of genes. Here we presented a systematic assessment of the temporal alternative splicing (AS) events during the critical development stages to capture the dynamic gene expression changes and AS in zebrafish. An unexpected transcriptome complexity generated by AS was observed during zebrafish development. The patterns of AS events varied substantially among developmental stages despite the similarities in the total proportion of AS genes. We further found that AS afforded substantial functional diversification of genes through the generation of stage-specific AS events from broadly protein-coding genes as an essential developmental regulatory mechanism. Skipped exon (SE) showed the strongest signals among developmental AS (devAS), suggesting that devAS events generated by SE may be necessary for the normal development of zebrafish. Most developmental genes regulated by AS mechanisms were not modulated in terms of their overall expression levels, indicating that AS shaped the transcriptome independently from transcriptional regulation during development. 128-cell stage was a critical stage for gene transcription during embryonic development. Splicing factors as an essential developmental regulator underwent AS in the potential autoregulatory feedback loop and expressed multiple isoforms. Thus, zebrafish development was shaped by an interplay of programs controlling gene expression levels and AS. Overall, we provided a global view of developmental patterns of AS during zebrafish development and revealed that AS transitions were the crucial regulatory component of zebrafish embryonic development.
许多脊椎动物基因产生多种转录变体，这些变体可能编码具有不同功能的蛋白质同工型，但各种发育阶段的转录组还未被很好地定义。确定正常发育过程中的转录组及其调控是破译基因在特定发育阶段功能的关键。在这里，我们系统地评估了关键发育阶段的时间性可变剪接 (AS) 事件，以捕捉斑马鱼中动态基因表达变化和 AS。在斑马鱼发育过程中观察到 AS 产生的出乎意料的转录组复杂性。尽管 AS 基因的总比例相似，但 AS 事件的模式在不同发育阶段存在很大差异。我们进一步发现，AS 通过从广泛的蛋白质编码基因中产生特定于阶段的 AS 事件，为基因提供了实质性的功能多样化，这是一种基本的发育调控机制。在发育性 AS（devAS）中，外显子跳过（SE）显示出最强的信号，表明由 SE 产生的 devAS 事件可能是斑马鱼正常发育所必需的。大多数受 AS 机制调控的发育基因在其总体表达水平方面没有被调节，这表明 AS 在发育过程中独立于转录调控塑造转录组。128 细胞阶段是胚胎发育过程中基因转录的关键阶段。剪接因子作为一种重要的发育调节剂经历了 AS，在潜在的自调节反馈回路中表达了多种同工型。因此，斑马鱼的发育是由控制基因表达水平和 AS 的程序相互作用塑造的。总的来说，我们提供了一个关于斑马鱼发育过程中 AS 发育模式的全局视图，并揭示了 AS 转换是斑马鱼胚胎发育的关键调控组成部分。
