Identification of alternate polyadenylation sites and analysis of their tissue distribution using EST data

Identification of alternate polyadenylation sites and analysis of their tissue distribution using EST data
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DOI:
10.1101/gr.190501
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发表时间:
2001-09-01
期刊:
影响因子:
7
通讯作者:
Gautheret, D
Gautheret, D
中科院分区:
生物学1区
文献类型:
--
作者:
Beaudoing, E;Gautheret, D

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交替多聚腺苷酸化影响大部分高等真核生物mRNA,产生具有可变长度的3 '末端的成熟转录物。这种变异在来自全基因组序列的当前转录本目录中表现不佳,主要是因为这种转录后事件在DNA水平上不能直接检测到。通过与EST数据库的比较,可以更好地理解所有mRNA的交替多聚化。然而,将EST与mRNA进行比较是一项困难的任务,容易受到内部引发的陷阱,即内含子序列、重复元件、嵌合EST或与旁系同源基因的EST匹配的存在。我们在这里提出了一个计算机程序,解决这些问题,并显示EST匹配的查询mRNA序列预测交替聚腺苷酸化,并建议图书馆的具体形式。输出突出显示有效的多聚腺苷酸化信号,可能的伪影来源,如mRNA序列中富含A的片段,并允许使用颜色代码直接可视化EST文库。系统地研究了EST文库中mRNA替代形式分布的统计偏差。大约1450个人类和200个小鼠的mRNA显示出这样的偏差,表明在每种情况下,组织或疾病特异性调节聚腺苷酸化。
Alternate polyadenylation affects a large fraction of higher eucaryote mRNAs, producing Mature transcripts with 3 ' ends of variable length. This variation is poorly represented in the Current transcript catalog derived from whole genome sequences, mostly because Such posttranscriptional events are not detectable directly at the DNA level. Alternate polydenylation of all mRNA is better understood by comparision to EST databases. Comparing ESTs to mRNAs, however, is a difficult task subjected to the pitfalls of internal priming I presence of intron sequences, repeated elements, chimerical ESTs or matches with EST from paralogous genes. We present here a computer program that addresses these problems and displays ESTs matches to a query mRNA sequence to predict alternate polyadenylation and to suggest library-specific forms. The Output highlights effective polyadenylation Signals, Possible Sources of artifacts such as A-rich stretches in the mRNA Sequences, and allows for a direct visualization of EST libraries using color codes. Statistical biases in the distribution of alternative mRNA forms among EST libraries were systematically Sought. About 1450 human and 200 Mouse mRNAs displayed such biases, suggesting in each case a tissue- or disease-specific regulation of polyadenylation.