Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
Biol Direct. 2011 May 18;6:24. doi: 10.1186/1745-6150-6-24.
The costs and benefits of spliceosomal introns in eukaryotes have not been established. One recognized effect of intron splicing is its known enhancement of gene expression. However, the mechanism regulating such splicing-mediated expression enhancement has not been defined. Previous studies have shown that intron splicing is a time-consuming process, indicating that splicing may not reduce the time required for transcription and processing of spliced pre-mRNA molecules; rather, it might facilitate the later rounds of transcription. Because the densities of active RNA polymerase II on most genes are less than one molecule per gene, direct interactions between the splicing apparatus and transcriptional complexes (from the later rounds of transcription) are infrequent, and thus unlikely to account for splicing-mediated gene expression enhancement.
The serine/arginine-rich protein SF2/ASF can inhibit the DNA topoisomerase I activity that removes negative supercoiling of DNA generated by transcription. Consequently, splicing could make genes more receptive to RNA polymerase II during the later rounds of transcription, and thus affect the frequency of gene transcription. Compared with the transcriptional enhancement mediated by strong promoters, intron-containing genes experience a lower frequency of cut-and-paste processes. The cleavage and religation activity of DNA strands by DNA topoisomerase I was recently shown to account for transcription-associated mutagenesis. Therefore, intron-mediated enhancement of gene expression could reduce transcription-associated genome instability.
Experimentally test whether transcription-associated mutagenesis is lower in intron-containing genes than in intronless genes. Use bioinformatic analysis to check whether exons flanking lost introns have higher frequencies of short deletions.
The mechanism of intron-mediated enhancement proposed here may also explain the positive correlation observed between intron size and gene expression levels in unicellular organisms, and the greater number of intron containing genes in higher organisms.
This article was reviewed by Dr Arcady Mushegian, Dr Igor B Rogozin (nominated by Dr I King Jordan) and Dr Alexey S Kondrashov. For the full reviews, please go to the Reviewer's Reports section.
真核生物中剪接体内含子的成本和收益尚未确定。内含子剪接的一个公认效果是已知的增强基因表达。然而，调节这种剪接介导的表达增强的机制尚未确定。先前的研究表明，内含子剪接是一个耗时的过程，这表明剪接可能不会减少拼接前 mRNA 分子转录和加工所需的时间；相反，它可能促进后来的转录轮次。由于大多数基因上活跃的 RNA 聚合酶 II 的密度小于每个基因一个分子，因此剪接装置与转录复合物（来自后来的转录轮次）之间的直接相互作用很少见，因此不太可能解释剪接介导的基因表达增强。
富含丝氨酸/精氨酸的蛋白 SF2/ASF 可以抑制去除转录产生的 DNA 负超螺旋的 DNA 拓扑异构酶 I 活性。因此，剪接可以使基因在后来的转录轮次中更容易接受 RNA 聚合酶 II，从而影响基因转录的频率。与由强启动子介导的转录增强相比，含有内含子的基因经历较低频率的“切-粘贴”过程。最近表明，DNA 拓扑异构酶 I 的 DNA 链的切割和连接活性导致转录相关的突变。因此，内含子介导的基因表达增强可以降低转录相关的基因组不稳定性。
实验测试内含子基因中的转录相关突变是否低于无内含子基因。使用生物信息学分析检查丢失内含子侧翼的外显子是否具有更高频率的短缺失。
这里提出的内含子介导的增强机制也可能解释在单细胞生物中观察到的内含子大小与基因表达水平之间的正相关，以及高等生物中更多包含内含子的基因。
本文由 Arcady Mushegian 博士、Igor B. Rogozin 博士（由 I. King Jordan 博士提名）和 Alexey S. Kondrashov 博士进行了评论。有关完整的评论，请转到评论者报告部分。
