Genome-wide detection of testis- and testicular cancer-specific alternative splicing
Genome-wide detection of testis- and testicular cancer-specific alternative splicing
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DOI：
10.1093/carcin/bgm194
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发表时间：
2007-12-01
期刊：
影响因子：
4.7
通讯作者：
Zhou, Rongjia
中科院分区：
文献类型：
--
作者：
He, Chunjiang;Zuo, Zhixiang;Zhou, Rongjia
选择性前信使RNA（mRNA）剪接是允许蛋白质多样性的关键分子事件，并且在发育和疾病中起重要作用。精子发生过程中的前体mRNA剪接调节和睾丸肿瘤发生中的前体mRNA剪接病因学尚待鉴定。通过全基因组分析，我们描述了人类睾丸、睾丸癌和小鼠睾丸之间的选择性剪接特征，以区分不同的选择性前体mRNA剪接模式。通过计算消减分析，我们检测到80睾丸特异性转录候选人在人类睾丸，175人睾丸癌和262小鼠睾丸，这是整合到一个数据库。逆转录-聚合酶链反应证实，这些候选转录本大多数是睾丸特异性的。大约40%的转录本来自未知/假设基因，这对于进一步的功能分析是有用的。这些转录本没有重叠，表明缺乏进化保守性。进一步的染色体定位显示了选择性前mRNA剪接事件的明显染色体偏好。比较分析表明，人睾丸肿瘤中前体mRNA选择性剪接与小鼠睾丸中前体mRNA选择性剪接具有一定的特征和趋势。此外，人类睾丸肿瘤倾向于使用罕见的剪接位点，并且在正常睾丸和睾丸肿瘤之间的优势剪接位点附近也存在不同的序列。人类睾丸肿瘤中选择性前mRNA剪接的这些特殊特征表明睾丸肿瘤的发生涉及多个步骤/水平的选择性剪接事件。选择性剪接作为睾丸肿瘤临床诊断、预后和治疗新策略的潜在来源，具有良好的前景。
Alternative pre-messenger RNA (mRNA) splicing is a key molecular event that allows for protein diversity and plays important roles in development and disease. Alternative pre-mRNA splicing regulations during spermatogenesis and alternative pre-mRNA splicing etiology in testicular tumorigenesis are yet to be characterized. By genome-wide analysis, here we describe alternative splicing features that distinguish distinctive patterns of alternative pre-mRNA splicing among human testis, testicular cancer and mouse testis. Through computationally subtractive analysis, we detected 80 testis-specific transcript candidates in human testis, 175 in human testicular cancer and 262 in mouse testis, which were integrated into a database. Reverse transcription-polymerase chain reaction confirmed that most of these transcript candidates from mouse testis were testis specific. Around 40% of the transcripts were from unknown/hypothetical genes, which were useful for further functional analysis. These transcripts were not overlapped, indicating lack of evolutionary conservation. Further chromosome mapping showed distinct chromosomal preference of alternative pre-mRNA splicing events. Comparison analysis indicated that alternative pre-mRNA splicing in human testicular tumor shared some characters/trends with those in mouse testis. Moreover, human testicular tumor tended to use rare splice sites and there were also distinct sequences adjacent dominant splice sites between normal testis and testicular tumor. These special features of alternative pre-mRNA splicing in human testicular tumor suggested that testicular tumorigenesis was involved in multiple steps/levels of alternative splicing events. Using alternative splicing as a potential source for new clinical diagnostic, prognostic and therapeutic strategies for treatment of testicular tumors seems to have a bright prospect.