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Genome Biol. 2016 Oct 25;17(1):220.

Transcriptome-wide effects of inverted SINEs on gene expression and their impact on RNA polymerase II activity.

Author information

1
Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Dr. Bohr Gasse 9/5, Vienna, A-1030, Austria.
2
Institute for Theoretical Chemistry, University of Vienna, Währinger Strasse 17, Vienna, A-1090, Austria.
3
Department of Cell and Developmental Biology, Medical University of Vienna, Schwarzspanierstrasse 17, Vienna, A-1090, Austria.
4
Present address: Center for molecular biology of the University Heidelberg, Im Neuenheimer Feld 282, Heidelberg, D-69120, Germany.
5
Department of Cell and Developmental Biology, Medical University of Vienna, Schwarzspanierstrasse 17, Vienna, A-1090, Austria. Michael.Jantsch@meduniwien.ac.at.
6
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.

Abstract

BACKGROUND:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

ADAR; Alu elements; Double-stranded RNA; Gene regulation; RNA Pol II; RNA editing; SINE; Transcription

PMID:
27782844
PMCID:
PMC5080714
DOI:
10.1186/s13059-016-1083-0
[Indexed for MEDLINE]
Free PMC Article

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