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首页> 外文期刊>Nucleic Acids Research >Global regulation of alternative splicing during myogenic differentiation
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Global regulation of alternative splicing during myogenic differentiation

机译：在成肌分化过程中选择性剪接的全球调控

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Recent genome-wide analyses have elucidated the extent of alternative splicing (AS) in mammals, often focusing on comparisons of splice isoforms between differentiated tissues. However, regulated splicing changes are likely to be important in biological transitions such as cellular differentiation, or response to environmental stimuli. To assess the extent and significance of AS in myogenesis, we used splicing-sensitive microarray analysis of differentiating C2C12 myoblasts. We identified 95 AS events that undergo robust splicing transitions during C2C12 differentiation. More than half of the splicing transitions are conserved during differentiation of avian myoblasts, suggesting the products and timing of transitions are functionally significant. The majority of splicing transitions during C2C12 differentiation fall into four temporal patterns and were dependent on the myogenic program, suggesting that they are integral components of myogenic differentiation. Computational analyses revealed enrichment of many sequence motifs within the upstream and downstream intronic regions near the alternatively spliced regions corresponding to binding sites of splicing regulators. Western analyses demonstrated that several splicing regulators undergo dynamic changes in nuclear abundance during differentiation. These findings show that within a developmental context, AS is a highly regulated and conserved process, suggesting a major role for AS regulation in myogenic differentiation.
机译：最近的全基因组分析阐明了哺乳动物中选择性剪接（AS）的程度，通常侧重于分化组织之间剪接同工型的比较。但是，调节的剪接变化在诸如细胞分化或对环境刺激的反应等生物学转变中可能很重要。为了评估AS在肌发生中的程度和意义，我们使用了区分C2C12成肌细胞的剪接敏感微阵列分析。我们确定了95个AS事件在C2C12分化过程中经历了强大的剪接过渡。禽成肌细胞分化过程中超过一半的剪接过渡是保守的，这表明过渡的产物和时机在功能上很重要。 C2C12分化过程中的大多数剪接过渡都分为四个时间模式，并且依赖于成肌程序，表明它们是成肌分化的组成部分。计算分析表明，在对应于剪接调节子结合位点的交替剪接区域附近的上游和下游内含子区域内，许多序列基序的富集。西方分析表明，一些剪接调节子在分化过程中经历了核丰度的动态变化。这些发现表明，在发育的背景下，AS是一个高度调节和保守的过程，表明AS调节在成肌分化中的重要作用。

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