Extensive relationship between antisense transcription and alternative splicing in the human genome
Extensive relationship between antisense transcription and alternative splicing in the human genome
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DOI：
10.1101/gr.113431.110
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发表时间：
2011-08-01
期刊：
影响因子：
7
通讯作者：
Marra, Marco A.
中科院分区：
文献类型：
--
作者：
Morrissy, A. Sorana;Griffith, Malachi;Marra, Marco A.
为了分析反义转录和选择性剪接之间的关系，我们开发了一种计算方法，用于检测反义相关的外显子剪接事件，使用Affytron外显子阵列数据。我们对176个淋巴母细胞样细胞系的表达数据的分析显示，大多数表达的有义反义基因表现出与反义基因表达相关的选择性剪接事件。这些事件大多发生在有义反义（SAS）基因重叠的区域，相对于相同基因的非重叠区域，这些区域在外显子和核小体占用水平上都显着富集。核小体占有率与重叠区域的Pol II丰度高度相关，并且伴随着局部替代外显子使用的增加。这些结果与正常人细胞中反义转录介导的剪接调节机制一致。比较摩门教与非洲裔个体之间反义相关剪接事件的患病率，揭示了可能表明新SAS基因座持续进化的人群特异性事件。此外，反义转录的存在与多个后生动物物种的选择性剪接相关，这表明它可能是一种保守的剪接调节机制。
To analyze the relationship between antisense transcription and alternative splicing, we developed a computational approach for the detection of antisense-correlated exon splicing events using Affymetrix exon array data. Our analysis of expression data from 176 lymphoblastoid cell lines revealed that the majority of expressed sense-antisense genes exhibited alternative splicing events that were correlated to the expression of the antisense gene. Most of these events occurred in areas of sense-antisense (SAS) gene overlap, which were significantly enriched in both exons and nucleosome occupancy levels relative to nonoverlapping regions of the same genes. Nucleosome occupancy was highly correlated with Pol II abundance across overlapping regions and with concomitant increases in local alternative exon usage. These results are consistent with an antisense transcription-mediated mechanism of splicing regulation in normal human cells. A comparison of the prevalence of antisense-correlated splicing events between individuals of Mormon versus African descent revealed population-specific events that may indicate the continued evolution of new SAS loci. Furthermore, the presence of antisense transcription was correlated to alternative splicing across multiple metazoan species, suggesting that it may be a conserved mechanism contributing to splicing regulation.