Variation in alternative splicing across human tissues.
Variation in alternative splicing across human tissues.
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DOI：
10.1186/gb-2004-5-10-r74
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发表时间：
2004
期刊：
影响因子：
12.3
通讯作者：
Burge CB
中科院分区：
文献类型：
--
作者：
Yeo G;Holste D;Kreiman G;Burge CB
对基因组比对ESTs的选择性剪接模式的分析表明，人脑、睾丸和肝脏具有异常高水平的选择性剪接，并确定了可能在人类细胞组织特异性选择性剪接中发挥重要作用的候选顺式作用因子。选择性前mrna剪接（AS）被高等真核生物广泛用于在特定的细胞或组织类型中产生不同的蛋白质亚型。为了比较不同人体组织的AS事件，我们分析了来自不同组织的cdna文库的基因组对齐表达序列标签（ESTs）的剪接模式。控制不同组织间EST覆盖范围的差异，我们发现大脑和睾丸具有最高水平的外显子跳跃。不同组织之间最显著的差异是3‘剪接位点和5’剪接位点的使用频率，肝脏中3‘剪接位点和5’剪接位点的使用频率比所研究的任何其他人体组织高约50%至100%。通过对剪接连接使用的差异进行量化，发现脑、胰腺、肝脏和周围神经系统具有最明显的AS模式。对现有微阵列表达数据的分析显示，与所研究的其他人体组织相比，肝脏的丝氨酸-精氨酸蛋白和异质核糖核蛋白基因的表达模式差异最大，这可能是肝脏中使用选择性剪接位点频率异常高的原因。在大脑、睾丸和肝脏中表达的基因外显子中富集的序列基序表明，特定的剪接因子可能在这些组织中的AS调节中起重要作用。本研究区分了人类大脑、睾丸和肝脏具有异常高水平的as，突出了不同组织中常见as类型的差异，并确定了可能在人类细胞组织特异性as中发挥重要作用的候选顺式调控元件和反式作用因子。
Analysis of the alternative splicing patterns of genomically aligned ESTs revealed that human brain, testis and liver have unusually high levels of alternative splicing and identified candidate cis-acting factors likely to play important roles in tissue-specific alternative splicing in human cells. Alternative pre-mRNA splicing (AS) is widely used by higher eukaryotes to generate different protein isoforms in specific cell or tissue types. To compare AS events across human tissues, we analyzed the splicing patterns of genomically aligned expressed sequence tags (ESTs) derived from libraries of cDNAs from different tissues. Controlling for differences in EST coverage among tissues, we found that the brain and testis had the highest levels of exon skipping. The most pronounced differences between tissues were seen for the frequencies of alternative 3' splice site and alternative 5' splice site usage, which were about 50 to 100% higher in the liver than in any other human tissue studied. Quantifying differences in splice junction usage, the brain, pancreas, liver and the peripheral nervous system had the most distinctive patterns of AS. Analysis of available microarray expression data showed that the liver had the most divergent pattern of expression of serine-arginine protein and heterogeneous ribonucleoprotein genes compared to the other human tissues studied, possibly contributing to the unusually high frequency of alternative splice site usage seen in liver. Sequence motifs enriched in alternative exons in genes expressed in the brain, testis and liver suggest specific splicing factors that may be important in AS regulation in these tissues. This study distinguishes the human brain, testis and liver as having unusually high levels of AS, highlights differences in the types of AS occurring commonly in different tissues, and identifies candidate cis-regulatory elements and trans-acting factors likely to have important roles in tissue-specific AS in human cells.
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影响因子：
7
作者：
Griffin, TJ;Gygi, SP;Aebersold, R
通讯作者：
Aebersold, R
影响因子：
5.8
作者：
Green, Richard E.;Lewis, Benjamin P.;Brenner, Steven E.
通讯作者：
Brenner, Steven E.
影响因子：
11.4
作者：
Caputi, M;Mayeda, A;Zahler, AM
通讯作者：
Zahler, AM
影响因子：
7
作者：
Hu, GK;Madore, SJ;Wang, YX
通讯作者：
Wang, YX
影响因子：
11.4
作者：
Caputi, M;Zahler, AM
通讯作者：
Zahler, AM