Mammalian mRNA splice-isoform selection is tightly controlled
Mammalian mRNA splice-isoform selection is tightly controlled
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DOI：
10.1534/genetics.106.066183
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发表时间：
2007-03-01
期刊：
影响因子：
3.3
通讯作者：
Burke, David T.
中科院分区：
文献类型：
--
作者：
Chisa, Jennifer L.;Burke, David T.
转录后RNA加工是决定真核细胞表型的重要调控机制。将转录的RNA物种加工成可选择的剪接异构体产生可以执行不同功能的产物。假定多细胞生物中的每种类型的细胞都能主动控制可选剪接异构体的相对数量。本研究采用定量反转录- pcr扩增技术检测了5个mRNA转录单位的互剪接异构体。我们表明，当在大量遗传多样性小鼠（即，完整的兄弟姐妹；N = 150）中测量时，剪接异构体选择的个体间变异受到非常高的限制。值得注意的是，剪接-异构体比率是在该种群中测量到的最不变的表型之一，并在第二个遗传上不同的种群中得到证实。此外，剪接异构体选择模式显示出组织特异性和年龄相关的变化。我们提出，剪接异构体选择对遗传和环境变异性具有特别强的鲁棒性，并可能为细胞稳态提供一个控制点。因此，剪接-异构体比率可以作为细胞和组织生理状态的实际定量测量。
Post-transcriptional RNA processing is an important regulatory control mechanism for determining the phenotype of eukaryotic cells. The processing of a transcribed RNA species into alternative splice isoforms yields products that can perform different functions. Each type of cell in a multi-cellular organism is presumed to actively control the relative quantities of alternative splice isoforms. In this study, the alternatively spliced isoforms of five mRNA transcription units were examined by quantitative reverse transcyiption-PCR amplification. We show that interindividual variation in splice-isoform selection is very highly constrained when measured in a large population of genetically diverse mice (i.e., full siblings; N = 150). Remarkably, splice-isoform ratios are among the most invariant phenotypes measured in this population and are confirmed in a second, genetically distinct population. In addition, the patterns of splice-isoform selection show tissue-specific and age-related changes. We propose that splice-isoform selection is exceptionally robust to genetic and environmental variability and may provide a control point for cellular homeostasis. As a consequence, splice-isoform ratios may be useful as a practical quantitative measure of the physiological status of cells and tissues.