science20121221-2

来自美国麻省理工学院的研究人员对4种哺乳动物和1种鸟类的cDNA进行了史无前例地深度测序,他们发现不同脊椎动物中的信使RNA的选择性剪接存在显著差异,且与胞内激酶信号途径相关。

-2012年12月21日《科学》

中文翻译


【题目】哺乳动物组织中同功异构基因的调控进化动力学规律

【译文】大多数哺乳动物的基因通过选择性剪接产生大量不同的信使RNAs,但是剪接的保守性程度还不清楚。为了研究哺乳动物组织特异性的转录组变化,本研究对来自4种哺乳动物和1种鸟类的cDNA进行了史无前例地深度测序,且具有3次生物学重复。尽管组织特异性的基因表达程序高度保守,但本研究发现仅一小部分组织中的选择性剪接是保守的,更多的表现为种系特异性。本研究鉴定到数以千计先前未知的、种系特异性的和保守的选择性外显子;广泛保守的选择性外显子具有结合MBNL、PTB、RBFOX、STAR和TIA家族剪接因子的特点,这暗示他们是哺乳动物的古老的剪接调节因子。本研究结果也表明选择性剪接也能影响蛋白质的磷酸化能力,从而限定蛋白质激酶的作用范围。

英文原稿


[Title]: Evolutionary Dynamics of Gene and Isoform Regulation in Mammalian Tissues

[Authors]: Jason Merkin, Caitlin Russell, Ping Chen, and Christopher B. Burge

[Abstract]: Most mammalian genes produce multiple distinct messenger RNAs through alternative splicing, but the extent of splicing conservation is not clear. To assess tissue-specific transcriptome variation across mammals, we sequenced complementary DNA from nine tissues from four mammals and one bird in biological triplicate, at unprecedented depth. We find that while tissue-specific gene expression programs are largely conserved, alternative splicing is well conserved in only a subset of tissues and is frequently lineage-specific. Thousands of previously unknown, lineage-specific, and conserved alternative exons were identified; widely conserved alternative exons had signatures of binding by MBNL, PTB, RBFOX, STAR, and TIA family splicing factors, implicating them as ancestral mammalian splicing regulators. Our data also indicate that alternative splicing often alters protein phosphorylatability, delimiting the scope of kinase signaling.

原文地址

http://www.sciencemag.org/content/338/6114/1593.abstract

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