Stochastic principles governing alternative splicing of RNA.
Stochastic principles governing alternative splicing of RNA.
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DOI：
10.1371/journal.pcbi.1005761
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发表时间：
2017-09
影响因子：
4.3
通讯作者：
Douek DC
中科院分区：
文献类型：
--
作者：
Hu J;Boritz E;Wylie W;Douek DC
主要转录异构体相对于来自通过选择性剪接（AS）产生的相同基因的其他异构体的优势对于维持正常细胞生理学是必不可少的。然而，决定这种支配地位的基本原则仍然不明。在这里，我们分析了物理AS过程，发现它可以通过随机最小化过程建模，这使得所有转录异构体的缩放表达水平遵循相同的Weibull极值分布。令人惊讶的是，我们还发现了一个简单的方程来描述不同优势的转录异构体的中位频率。这两个参数威布尔模型提供了所有转录基因的所有亚型的统计分布，并揭示了以前无法解释的意见，相对亚型表达来自这些原则。真核细胞内的可变RNA剪接使每个基因能够产生多种不同的成熟转录物，这些转录物进一步编码具有不同甚至相反功能的蛋白质。由特定基因产生的转录本异构体的相对频率对于维持正常细胞生理学是必不可少的;然而，支配这些频率的潜在机制和原理尚不清楚。我们分析了高纯度的人T细胞亚群中所有转录异构体的频率分布，并建立了一个简单的数学模型，基于选择性剪接的物理过程，它提供了管理这个过程的统计学原理。该模型与观察到的来自不同组织和细胞系的所有转录物同种型的表达水平和相对频率的分布非常匹配。值得注意的是，我们用这个模型来阐明许多以前无法解释的观察有关转录异构体表达。更重要的是，这个模型揭示了简单的统计原理的存在，这些原理可以应用于理解一个基本而复杂的生物过程，如选择性剪接。
The dominance of the major transcript isoform relative to other isoforms from the same gene generated by alternative splicing (AS) is essential to the maintenance of normal cellular physiology. However, the underlying principles that determine such dominance remain unknown. Here, we analyzed the physical AS process and found that it can be modeled by a stochastic minimization process, which causes the scaled expression levels of all transcript isoforms to follow the same Weibull extreme value distribution. Surprisingly, we also found a simple equation to describe the median frequency of transcript isoforms of different dominance. This two-parameter Weibull model provides the statistical distribution of all isoforms of all transcribed genes, and reveals that previously unexplained observations concerning relative isoform expression derive from these principles. Alternative RNA splicing within eukaryotic cells enables each gene to generate multiple different mature transcripts which further encode proteins with distinct or even opposing functions. The relative frequencies of the transcript isoforms generated by a particular gene are essential to the maintenance of normal cellular physiology; however, the underlying mechanisms and principles that govern these frequencies are unknown. We analyzed the frequency distribution of all transcript isoforms in highly purified human T cell subsets and built a simple mathematical model, based on the physical process of alternative splicing, which provides statistical principles that govern this process. This model matches very well with the observed distributions of expression levels and relative frequencies of all transcript isoforms from different tissues and cell lines. Notably, we used this model to elucidate many previously unexplained observations concerning transcript isoform expression. More importantly, this model reveals the existence of simple statistical principles that can be applied to understanding an essential and complex biological process such as alternative splicing.
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影响因子：
12.3
作者：
Gonzàlez-Porta M;Frankish A;Rung J;Harrow J;Brazma A
通讯作者：
Brazma A
DOI：
10.3390/v5061571
发表时间：
2013-06-21
期刊：
Viruses
影响因子：
--
作者：
Boehm D;Conrad RJ;Ott M
通讯作者：
Ott M
影响因子：
46.9
作者：
Trapnell C;Williams BA;Pertea G;Mortazavi A;Kwan G;van Baren MJ;Salzberg SL;Wold BJ;Pachter L
通讯作者：
Pachter L
影响因子：
46.9
作者：
Patro, Rob;Mount, Stephen M.;Kingsford, Carl
通讯作者：
Kingsford, Carl
影响因子：
3.7
作者：
Plowman, SJ;Arends, MJ;Patek, CE
通讯作者：
Patek, CE