Tajaddod Mansoureh, Tanzer Andrea, Licht Konstantin, Wolfinger Michael T, Badelt Stefan, Huber Florian, Pusch Oliver, Schopoff Sandy, Janisiw Michael, Hofacker Ivo, Jantsch Michael F
Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Dr. Bohr Gasse 9/5, Vienna, A-1030, Austria.
Institute for Theoretical Chemistry, University of Vienna, Währinger Strasse 17, Vienna, A-1090, Austria.
Genome Biol. 2016 Oct 25;17(1):220. doi: 10.1186/s13059-016-1083-0.
Short interspersed elements (SINEs) represent the most abundant group of non-long-terminal repeat transposable elements in mammalian genomes. In primates, Alu elements are the most prominent and homogenous representatives of SINEs. Due to their frequent insertion within or close to coding regions, SINEs have been suggested to play a crucial role during genome evolution. Moreover, Alu elements within mRNAs have also been reported to control gene expression at different levels.
Here, we undertake a genome-wide analysis of insertion patterns of human Alus within transcribed portions of the genome. Multiple, nearby insertions of SINEs within one transcript are more abundant in tandem orientation than in inverted orientation. Indeed, analysis of transcriptome-wide expression levels of 15 ENCODE cell lines suggests a cis-repressive effect of inverted Alu elements on gene expression. Using reporter assays, we show that the negative effect of inverted SINEs on gene expression is independent of known sensors of double-stranded RNAs. Instead, transcriptional elongation seems impaired, leading to reduced mRNA levels.
Our study suggests that there is a bias against multiple SINE insertions that can promote intramolecular base pairing within a transcript. Moreover, at a genome-wide level, mRNAs harboring inverted SINEs are less expressed than mRNAs harboring single or tandemly arranged SINEs. Finally, we demonstrate a novel mechanism by which inverted SINEs can impact on gene expression by interfering with RNA polymerase II.
短散在元件（SINEs）是哺乳动物基因组中最丰富的非长末端重复转座元件组。在灵长类动物中，Alu元件是SINEs最突出且最具同质性的代表。由于它们频繁插入编码区域内或附近，有人提出SINEs在基因组进化过程中发挥关键作用。此外，也有报道称mRNA中的Alu元件可在不同水平上控制基因表达。
在此，我们对人类Alu元件在基因组转录区域内的插入模式进行了全基因组分析。一个转录本内多个相邻的SINEs插入以串联方向比以反向方向更为丰富。实际上，对15个ENCODE细胞系全转录组表达水平的分析表明，反向Alu元件对基因表达具有顺式抑制作用。通过报告基因检测，我们表明反向SINEs对基因表达的负面影响独立于已知的双链RNA传感器。相反，转录延伸似乎受到损害，导致mRNA水平降低。
我们的研究表明，对于能够促进转录本内分子内碱基配对的多个SINEs插入存在偏向性。此外，在全基因组水平上，含有反向SINEs的mRNA比含有单个或串联排列的SINEs的mRNA表达量更低。最后，我们证明了一种新机制，即反向SINEs可通过干扰RNA聚合酶II来影响基因表达。
