Gallegos Jenna E, Rose Alan B
Department of Molecular and Cellular Biology, University of California, 1 Shields Avenue, Davis, CA, USA.
Plant Sci. 2015 Aug;237:8-15. doi: 10.1016/j.plantsci.2015.04.017. Epub 2015 Apr 30.
Within two years of their discovery in 1977, introns were found to have a positive effect on gene expression. Numerous examples of stimulatory introns have been described since then in very diverse organisms, including plants. In some cases, the mechanism through which the intron affects expression is readily understood. However, many introns that affect expression increase mRNA accumulation through an unknown mechanism, referred to as intron-mediated enhancement (IME). Despite several decades of research into IME, and the clear benefits of using introns to increase transgene expression, little progress has been made in understanding the mechanism of IME. Several fundamental questions regarding the role of transcription and splicing, the sequences responsible for IME, the involvement of other factors, and the relationship between introns and promoters remain unanswered. The more we learn about the properties of stimulating introns, the clearer it becomes that the effects of introns are unfamiliar and difficult to reconcile with conventional views of how transcription is controlled. We hypothesize that introns increase transcript initiation upstream of themselves by creating a localized region of accessible chromatin. Introns might represent a novel kind of downstream regulatory element for genes transcribed by RNA polymerase II.
1977年被发现后的两年内，内含子被发现对基因表达有积极影响。从那时起，在包括植物在内的多种生物中描述了许多刺激性内含子的例子。在某些情况下，内含子影响表达的机制很容易理解。然而，许多影响表达的内含子通过一种未知机制增加mRNA积累，这种机制被称为内含子介导的增强作用（IME）。尽管对IME进行了几十年的研究，并且使用内含子增加转基因表达有明显的好处，但在理解IME机制方面进展甚微。关于转录和剪接的作用、负责IME的序列、其他因素的参与以及内含子与启动子之间的关系等几个基本问题仍未得到解答。我们对刺激性内含子的特性了解得越多，就越清楚内含子的作用是陌生的，并且难以与转录调控的传统观点相协调。我们假设内含子通过创建一个可及染色质的局部区域来增加其自身上游的转录起始。内含子可能代表了一种新型的由RNA聚合酶II转录的基因的下游调控元件。
