Alternative isoform regulation in human tissue transcriptomes.
Alternative isoform regulation in human tissue transcriptomes.
复制标题
DOI：
10.1038/nature07509
复制
发表时间：
2008-11-27
期刊：
影响因子：
64.8
通讯作者：
Burge, Christopher B.
中科院分区：
文献类型：
--
作者：
Wang, Eric T.;Sandberg, Rickard;Luo, Shujun;Khrebtukova, Irina;Zhang, Lu;Mayr, Christine;Kingsmore, Stephen F.;Schroth, Gary P.;Burge, Christopher B.
通过对前体mRNA的可变加工，单个哺乳动物基因常常产生多种mRNA和蛋白质异构体，它们可能具有相关、不同甚至相反的功能。在此，我们报告了基于cDNA片段深度测序对15种不同的人类组织和细胞系转录组进行的深入分析，得到了基因和mRNA异构体表达的数字化清单。对序列读取到外显子 - 外显子连接的定位分析表明，92 - 94%的人类基因经历可变剪接（AS），约86%的基因其次要异构体频率为15%或更高。异构体特异性读取密度的差异表明，大多数可变剪接以及可变切割和多聚腺苷酸化（APA）事件在不同组织之间存在差异，而个体之间的差异约少2 - 3倍。组织之间剪接的极端或“开关样”调控与调控区域的序列保守性增加以及全长开放阅读框的产生相关。可变剪接和多聚腺苷酸化的模式在不同组织之间密切相关，这表明这些过程受到协同调控，并且在可变内含子和3′非翻译区中一部分已知调控基序的序列保守性表明特定因子共同参与了剪接和多聚腺苷酸化在组织水平的调控。
Through alternative processing of pre-mRNAs, individual mammalian genes often produce multiple mRNA and protein isoforms that may have related, distinct or even opposing functions. Here we report an in-depth analysis of 15 diverse human tissue and cell line transcriptomes based on deep sequencing of cDNA fragments, yielding a digital inventory of gene and mRNA isoform expression. Analysis of mappings of sequence reads to exon-exon junctions indicated that 92-94% of human genes undergo alternative splicing (AS), ∼86% with a minor isoform frequency of 15% or more. Differences in isoform-specific read densities indicated that a majority of AS and of alternative cleavage and polyadenylation (APA) events vary between tissues, while variation between individuals was ∼2- to 3-fold less common. Extreme or ‘switch-like’ regulation of splicing between tissues was associated with increased sequence conservation in regulatory regions and with generation of full-length open reading frames. Patterns of AS and APA were strongly correlated across tissues, suggesting coordinated regulation of these processes, and sequence conservation of a subset of known regulatory motifs in both alternative introns and 3′ UTRs suggested common involvement of specific factors in tissue-level regulation of both splicing and polyadenylation.
登录
查看更多内容
影响因子：
4.4
作者：
Gupta S;Zink D;Korn B;Vingron M;Haas SA
通讯作者：
Haas SA
影响因子：
14.9
作者：
通讯作者：
--
影响因子：
9.8
作者：
Mayr, Johannes A.;Merkel, Olaf;Sperl, Wolfgang
通讯作者：
Sperl, Wolfgang
影响因子：
5.3
作者：
McCracken, S;Lambermon, M;Blencowe, BJ
通讯作者：
Blencowe, BJ
影响因子：
5.3
作者：
Castelo-Branco, P;Furger, A;Proudfoot, N
通讯作者：
Proudfoot, N