An in-depth map of polyadenylation sites in cancer.
An in-depth map of polyadenylation sites in cancer.
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DOI：
10.1093/nar/gks637
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发表时间：
2012-09-01
影响因子：
14.9
通讯作者：
John B
中科院分区：
文献类型：
--
作者：
Lin Y;Li Z;Ozsolak F;Kim SW;Arango-Argoty G;Liu TT;Tenenbaum SA;Bailey T;Monaghan AP;Milos PM;John B
我们提供了一张超过100万个多聚腺苷酸化位点的综合图谱，并使用直接RNA测序方法量化了它们在主要癌症和肿瘤细胞系中的使用。我们建立了表达和多腺苷化数据库，以使各种癌症的多腺苷化图谱可视化，并促进发现对肿瘤发生有潜在重要作用的新基因和基因亚型。对多聚腺苷酸化位点的分析表明，很大一部分(∼30%)的mRNAs在其3‘非翻译区含有替代的多腺苷基化位点，与细胞类型无关。最短的3‘非翻译区亚型在全基因组的癌症组织中优先上调。选择性多聚腺苷介导的短异构体上调的候选靶点包括POLR2K，以及细胞-细胞和细胞-细胞外基质接触的信号级联，特别是涉及Rho GTP酶的调节因子。多聚腺苷化图谱还有助于改进3‘非翻译区的注释，并识别候选调控标记，如序列基序、H3K36me3和Pabpc1，这些标记依赖于异构体并以位置特异性的方式出现。总而言之，这些结果强调了需要超越仅仅监测一个基因的累积转录水平，而是单独分析其RNA异构体的表达。
We present a comprehensive map of over 1 million polyadenylation sites and quantify their usage in major cancers and tumor cell lines using direct RNA sequencing. We built the Expression and Polyadenylation Database to enable the visualization of the polyadenylation maps in various cancers and to facilitate the discovery of novel genes and gene isoforms that are potentially important to tumorigenesis. Analyses of polyadenylation sites indicate that a large fraction (∼30%) of mRNAs contain alternative polyadenylation sites in their 3′ untranslated regions, independent of the cell type. The shortest 3′ untranslated region isoforms are preferentially upregulated in cancer tissues, genome-wide. Candidate targets of alternative polyadenylation-mediated upregulation of short isoforms include POLR2K, and signaling cascades of cell–cell and cell–extracellular matrix contact, particularly involving regulators of Rho GTPases. Polyadenylation maps also helped to improve 3′ untranslated region annotations and identify candidate regulatory marks such as sequence motifs, H3K36Me3 and Pabpc1 that are isoform dependent and occur in a position-specific manner. In summary, these results highlight the need to go beyond monitoring only the cumulative transcript levels for a gene, to separately analysing the expression of its RNA isoforms.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
11.4
作者：
Alberts, AS;Treisman, R
通讯作者：
Treisman, R
DOI：
10.1007/978-1-61779-005-8_25
发表时间：
2011-01-01
期刊：
RNA DETECTION AND VISUALIZATION: METHODS AND PROTOCOLS
影响因子：
--
作者：
Jayaseelan, Sabarinath;Doyle, Francis;Tenenbaum, Scott A.
通讯作者：
Tenenbaum, Scott A.
影响因子：
7
作者：
Beaudoing, E;Gautheret, D
通讯作者：
Gautheret, D
影响因子：
4.5
作者：
Lee, Kwanbok;Kunkeaw, Nawapol;Lee, Yong Sun
通讯作者：
Lee, Yong Sun