促进器的方向性是由U1 snRNP和多基化信号控制的
Albert E Almada1, Xuebing Wu, Andrea J Kriz
1David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nature
|June 25, 2013
概括
一个新的U1-PAS轴控制基因转录方向性. 这种机制使用序列元素来促进反意义RNA的早期终止,限制普遍转录并确保生产性基因表达.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 基因法规 基因法规
背景情况:
- 哺乳动物基因组转录是普遍存在的,但生产性转录受到未知的机制的限制.
- RNA聚合酶II (RNAPII) 与大多数促进体不同的启动,但延伸主要发生在感觉编码方向.
研究的目的:
- 研究控制促销者定向和生产转录的机制.
- 为了确定调节促剂-近位裂变和多基化的序列决定因素.
主要方法:
- 对小鼠胚胎干细胞的分析.
- 对横跨转录起始点的序列决定因素进行de novo动机分析.
- 功能性破坏U1小核核糖核蛋白 (snRNP) 活动.
主要成果:
- 不对称的序列决定因素通过促进者-近位裂变和多基化来调节促进者的方向性.
- 上游反意义RNAs在启动后不久被分裂和多化.
- U1 snRNP识别站点和多个站点 (PAS) 信号在感觉和反感觉方向上有差异分布,并且随着时间的推移而演变.
- 破坏U1 snRNP活动会增加促销器-近端裂变事件.
结论:
- 一个U1-PAS轴通过促进上游反意义转录的早期终止来加强促进器的方向性.
- 这个轴通过通过U1 snRNP抑制近位感PAS信号来限制整个基因组的普遍转录.
- 这些发现揭示了一种用于控制全基因组转录的新型调节机制.
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