title: Transcriptome-wide effects of inverted SINEs on gene expression and their impact on RNA polymerase II activity.
abstract: 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.
authors: Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Dr. Bohr Gasse 9/5, Vienna, A-1030, Austria.
authors: Mansoureh
authors: M
authors: Tajaddod
authors: Institute for Theoretical Chemistry, University of Vienna, Währinger Strasse 17, Vienna, A-1090, Austria.
authors: Andrea
authors: A
authors: Tanzer
authors: Department of Cell and Developmental Biology, Medical University of Vienna, Schwarzspanierstrasse 17, Vienna, A-1090, Austria.
authors: Konstantin
authors: K
authors: Licht
authors: Department of Cell and Developmental Biology, Medical University of Vienna, Schwarzspanierstrasse 17, Vienna, A-1090, Austria.|Institute for Theoretical Chemistry, University of Vienna, Währinger Strasse 17, Vienna, A-1090, Austria.
authors: Michael T
authors: MT
authors: Wolfinger
authors: Institute for Theoretical Chemistry, University of Vienna, Währinger Strasse 17, Vienna, A-1090, Austria.
authors: Stefan
authors: S
authors: Badelt
authors: Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Dr. Bohr Gasse 9/5, Vienna, A-1030, Austria.|Present address: Center for molecular biology of the University Heidelberg, Im Neuenheimer Feld 282, Heidelberg, D-69120, Germany.
authors: Florian
authors: F
authors: Huber
authors: Department of Cell and Developmental Biology, Medical University of Vienna, Schwarzspanierstrasse 17, Vienna, A-1090, Austria.
authors: Oliver
authors: O
authors: Pusch
authors: Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Dr. Bohr Gasse 9/5, Vienna, A-1030, Austria.
authors: Sandy
authors: S
authors: Schopoff
authors: Department of Cell and Developmental Biology, Medical University of Vienna, Schwarzspanierstrasse 17, Vienna, A-1090, Austria.
authors: Michael
authors: M
authors: Janisiw
authors: Institute for Theoretical Chemistry, University of Vienna, Währinger Strasse 17, Vienna, A-1090, Austria.
authors: Ivo
authors: I
authors: Hofacker
authors: Department of Cell and Developmental Biology, Medical University of Vienna, Schwarzspanierstrasse 17, Vienna, A-1090, Austria. Michael.Jantsch@meduniwien.ac.at.|Department of Cell and Developmental Biology, Medical University of Vienna, Center of Anatomy and Cell Biology, Schwarzspanierstrasse 17, Vienna, A-1090, Austria. Michael.Jantsch@meduniwien.ac.at.
authors: Michael F
authors: MF
authors: Jantsch
mesh_terms: D020087:Alu Elements / Q000235:genetics; D002460:Cell Line; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D012319:RNA Polymerase II / Q000235:genetics*; D012330:RNA, Double-Stranded / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020086:Short Interspersed Nucleotide Elements / Q000235:genetics*; D014158:Transcription, Genetic; D059467:Transcriptome / Q000235:genetics*
chemical_list: D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D012319:RNA Polymerase II
keywords: ADAR; Alu elements; Double-stranded RNA; Gene regulation; RNA Pol II; RNA editing; SINE; Transcription