Impact of alternative initiation, splicing, and termination on the diversity of the mRNA transcripts encoded by the mouse transcriptome

Impact of alternative initiation, splicing, and termination on the diversity of the mRNA transcripts encoded by the mouse transcriptome
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DOI:
10.1101/gr.1017303
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发表时间:
2003-06-01
期刊:
影响因子:
7
通讯作者:
Gaasterland, T
Gaasterland, T
中科院分区:
生物学1区
文献类型:
--
作者:
Zavolan, M;Kondo, S;Gaasterland, T

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我们分析了60,770个RIKEN小鼠全长c DNA序列和44,122个公共m RNA序列的FANTOM2克隆集。我们开发了一种新的计算程序来识别和分类该数据集中明显的剪接变异形式,并将结果组织到一个可公开访问的数据库中,该数据库可用于未来的表达阵列构建、结构基因组学以及对选择性剪接的机制和调控的分析。统计分析表明,小鼠体内至少有41%甚至60%的多外显子基因具有多种剪接形式。在具有多种剪接形式的转录单位中,49%含有转录本,在转录本中,明显使用替代转录开始(停止)伴随着起始(末端)外显子的替代剪接。这意味着选择性转录可能经常诱导选择性剪接。有剪接变异的所有外显子中有73%落在注释编码区,这表明大多数剪接变异可能会影响蛋白质的形式。最后,我们比较了组成外显子集(存在于所有转录本中)和隐蔽外显子集(仅存在于某些转录本中),发现它们在长度分布、剪接接头周围的核苷酸分布以及几个短序列基序的出现频率方面存在显著差异。
We analyzed the FANTOM2 clone set of 60,770 RIKEN full-length mouse cDNA sequences and 44,122 public mRNA sequences. We developed a new computational procedure to identify and classify the forms of splice variation evident in this data set and organized the results into a publicly accessible database that can be used for future expression array construction, structural genomics, and analyses of the mechanism and regulation of alternative splicing. Statistical analysis shows that at least 41% and possibly as much as 60% of multiexon genes in mouse have multiple splice forms. Of the transcription units with multiple splice forms, 49% contain transcripts in which the apparent use of an alternative transcription start (stop) is accompanied by alternative splicing of the initial (terminal) exon. This implies that alternative transcription may frequently induce alternative splicing. The fact that 73% of all exons with splice variation fall within the annotated coding region indicates that most splice variation is likely to affect the protein form. Finally, we compared the set of constitutive (present in all transcripts) exons with the set of cryptic (present only in some transcripts) exons and found statistically significant differences in their length distributions, the nucleoticle distributions around their splice junctions, and the frequencies of occurrence of several short sequence motifs.