Deciphering the splicing code
Deciphering the splicing code
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DOI：
10.1038/nature09000
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发表时间：
2010-05-06
期刊：
影响因子：
64.8
通讯作者：
Frey, Brendan J.
中科院分区：
文献类型：
--
作者：
Barash, Yoseph;Calarco, John A.;Frey, Brendan J.
选择性剪接在生物复杂性的产生中起着至关重要的作用，其调控不当经常与人类疾病有关。在这里，我们描述了“剪接密码”的组装，它使用数百个RNA特征的组合来预测数千个外显子的选择性剪接中与组织相关的变化。该代码确定新的剪接模式类别，识别不同组织中不同的调控程序，并识别突变验证的调控序列。广泛的调控策略被揭示，包括使用出人意料的大量特征组合，建立被特定组织中的特征克服的低外显子包涵体水平，出现比先前所认识的更深入内含子的特征，以及通过转录本结构特征调节剪接变体水平。该密码检测到一类外显子，其包含通过激活无义介导的信使RNA衰退而在成年组织中沉默表达，但其排除促进了胚胎发育期间的表达。该密码有助于在全基因组范围内发现和详细描述受调控的选择性剪接事件。
Alternative splicing has a crucial role in the generation of biological complexity, and its misregulation is often involved in human disease. Here we describe the assembly of a 'splicing code', which uses combinations of hundreds of RNA features to predict tissue-dependent changes in alternative splicing for thousands of exons. The code determines new classes of splicing patterns, identifies distinct regulatory programs in different tissues, and identifies mutation-verified regulatory sequences. Widespread regulatory strategies are revealed, including the use of unexpectedly large combinations of features, the establishment of low exon inclusion levels that are overcome by features in specific tissues, the appearance of features deeper into introns than previously appreciated, and the modulation of splice variant levels by transcript structure characteristics. The code detected a class of exons whose inclusion silences expression in adult tissues by activating nonsense-mediated messenger RNA decay, but whose exclusion promotes expression during embryogenesis. The code facilitates the discovery and detailed characterization of regulated alternative splicing events on a genome-wide scale.