Wilmer Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Nucleic Acids Res. 2011 Oct;39(18):7920-30. doi: 10.1093/nar/gkr545. Epub 2011 Jun 30.
Alternative processing of pre-mRNA plays an important role in protein diversity and biological function. Previous studies on alternative splicing (AS) often focused on the spatial patterns of protein isoforms across different tissues. Here we studied dynamic usage of AS across time, during murine retina development. Over 7000 exons showed dynamical changes in splicing, with differential splicing events occurring more frequently in early development. The overall splicing patterns for exclusive and inclusive exons show symmetric trends and genes with symmetric splicing patterns that tend to have similar biological functions. Furthermore, we observed that within the retina, retina-enriched genes that are preferentially expressed at the adult stage tend to have more dynamically spliced exons compared to other genes, suggesting that genes maintaining retina homeostasis also play an important role in development via a series of AS events. Interestingly, the transcriptomes of retina-enriched genes largely reflect the retinal developmental process. Finally, we identified a number of candidate cis-regulatory elements for retinal AS by analyzing the relative occurrence of sequence motifs in exons or flanking introns. The occurrence of predicted regulatory elements showed strong correlation with the expression level of known RNA binding proteins, suggesting the high quality of the identified cis-regulatory elements.
前体 mRNA 的选择性加工在蛋白质多样性和生物学功能中起着重要作用。以前关于选择性剪接 (AS) 的研究通常集中在不同组织中蛋白质同工型的空间模式上。在这里，我们研究了在小鼠视网膜发育过程中，AS 随时间的动态变化。超过 7000 个外显子显示出剪接的动态变化，早期发育中差异剪接事件更频繁发生。排除和包含外显子的整体剪接模式显示出对称的趋势，具有对称剪接模式的基因往往具有相似的生物学功能。此外，我们观察到，在视网膜中，在成年阶段优先表达的富含视网膜的基因与其他基因相比，其外显子的剪接更具动态性，这表明维持视网膜内稳态的基因也通过一系列 AS 事件在发育中发挥重要作用。有趣的是，富含视网膜的基因的转录组在很大程度上反映了视网膜的发育过程。最后，我们通过分析外显子或侧翼内含子中序列基序的相对出现，鉴定了一些候选视网膜 AS 的顺式调控元件。预测调控元件的出现与已知 RNA 结合蛋白的表达水平具有很强的相关性，这表明所鉴定的顺式调控元件具有很高的质量。
