Shaul Orit
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
Int J Biochem Cell Biol. 2017 Oct;91(Pt B):145-155. doi: 10.1016/j.biocel.2017.06.016. Epub 2017 Jul 1.
In many eukaryotes, including mammals, plants, yeast, and insects, introns can increase gene expression without functioning as a binding site for transcription factors. This phenomenon was termed 'intron-mediated enhancement'. Introns can increase transcript levels by affecting the rate of transcription, nuclear export, and transcript stability. Moreover, introns can also increase the efficiency of mRNA translation. This review discusses the current knowledge about these processes. The role of splicing in IME and the significance of intron position relative to the sites of transcription and translation initiation are elaborated. Particular emphasis is placed on the question why different introns, present at the same location of the same genes and spliced at a similar high efficiency, can have very different impacts on expression - from almost no effect to considerable stimulation. This situation can be at least partly accounted for by the identification of splicing-unrelated intronic elements with a special ability to enhance mRNA accumulation or translational efficiency. The many factors that could lead to the large variation observed between the impact of introns in different genes and experimental systems are highlighted. It is suggested that there is no sole, definite answer to the question "how do introns enhance gene expression". Rather, each intron-gene combination might undergo its own unique mixture of processes that lead to the perceptible outcome.
在包括哺乳动物、植物、酵母和昆虫在内的许多真核生物中,内含子能够在不充当转录因子结合位点的情况下增加基因表达。这一现象被称为“内含子介导的增强作用”。内含子可通过影响转录速率、核输出和转录本稳定性来提高转录水平。此外,内含子还能提高mRNA翻译的效率。本综述讨论了有关这些过程的现有知识。阐述了剪接在内含子介导的增强作用中的作用以及内含子相对于转录和翻译起始位点的位置的重要性。特别强调了这样一个问题:为什么存在于同一基因相同位置且剪接效率相似的不同内含子,对基因表达的影响却大不相同——从几乎没有影响到显著的刺激作用。通过鉴定具有增强mRNA积累或翻译效率特殊能力的与剪接无关的内含子元件,这种情况至少可以部分得到解释。文中强调了许多可能导致不同基因和实验系统中内含子影响差异巨大的因素。有人提出,对于“内含子如何增强基因表达”这个问题,没有唯一确定的答案。相反,每个内含子与基因的组合可能经历其独特的一系列过程,从而导致可察觉的结果。