哺乳动物组织中基因和异形调节的进化动态
Jason Merkin1, Caitlin Russell, Ping Chen
1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Science (New York, N.Y.)
|December 22, 2012
概括
大多数哺乳动物的基因表达在整个组织中被保存,但替代的拼接模式因血统而异. 研究人员确定了新的拼接元素和关键的调节因素,揭示了对基因调节进化的洞察力.
科学领域:
- 进行比较的基因组学.
- 分子生物学分子生物学
- 进化生物学是进化的生物学.
背景情况:
- 替代拼接从哺乳动物基因中产生多种不同的信使RNA (mRNA).
- 跨哺乳动物组织和物种的替代拼接的保护在很大程度上仍然没有特征.
研究的目的:
- 研究跨哺乳动物血统的组织特异性替代拼接的保护.
- 为了识别新的替代拼接外子和保存拼接调节元素.
主要方法:
- 从四种哺乳动物和一只鸟类的九种组织中深度测序互补DNA (cDNA).
- 生物信息分析以识别保存和谱系特定的替代拼接事件.
- 分析与保存的替代外显子相关的序列动图,以推断调节因素.
主要成果:
- 组织特异性基因表达程序在哺乳动物中在很大程度上得到保护.
- 替代拼接在组织的子集中得到保存,频繁出现特定于血统的模式.
- 发现了成千上万的新型血统特异性和保存的替代前子.
- 保存的替代外显子显示了MBNL,PTB,RBFOX,STAR和TIA拼接因子的结合签名.
- 替代拼接经常影响蛋白质的酸化性,可能限制激酶信号通路.
结论:
- 替代拼接调节在哺乳动物血统中演变得不同.
- 像MBNL,PTB,RBFOX,STAR和TIA这样的拼接因素可能是哺乳动物替代拼接的古代调节者.
- 替代拼接在调节蛋白质功能和细胞信号网络方面发挥着重要作用.
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