@Article{Aktas_Avsar_Ilik_Maticzka-DHX_suppr_RNA-2017,
  author =	 {Aktas, Tugce and Avsar Ilik, Ibrahim and Maticzka, Daniel 
                  and Bhardwaj, Vivek and Pessoa Rodrigues, Cecilia and 
                  Mittler, Gerhard and Manke, Thomas and Backofen, Rolf and 
                  Akhtar, Asifa},
  title =	 {{DHX9} suppresses {RNA} processing defects originating from 
                  the {Alu} invasion of the human genome},
  journal =	 {Nature},
  year =	 {2017},
  volume =	 {544},
  number =	 {7648},
  pages =	 {115-119},
  user =	 {backofen},
  pmid =	 {28355180},
  doi = 	 {10.1038/nature21715},
  issn = 	 {1476-4687},
  issn = 	 {0028-0836},
  abstract =	 {Transposable elements are viewed as 'selfish genetic 
                  elements', yet they contribute to gene regulation and genome 
                  evolution in diverse ways. More than half of the human 
                  genome consists of transposable elements. Alu elements 
                  belong to the short interspersed nuclear element (SINE) 
                  family of repetitive elements, and with over 1 million 
                  insertions they make up more than 10% of the human genome. 
                  Despite their abundance and the potential evolutionary 
                  advantages they confer, Alu elements can be mutagenic to the 
                  host as they can act as splice acceptors, inhibit 
                  translation of mRNAs and cause genomic instability. Alu 
                  elements are the main targets of the RNA-editing enzyme ADAR 
                  and the formation of Alu exons is suppressed by the nuclear 
                  ribonucleoprotein HNRNPC, but the broad effect of massive 
                  secondary structures formed by inverted-repeat Alu elements 
                  on RNA processing in the nucleus remains unknown. Here we 
                  show that DHX9, an abundant nuclear RNA helicase, binds 
                  specifically to inverted-repeat Alu elements that are 
                  transcribed as parts of genes. Loss of DHX9 leads to an 
                  increase in the number of circular-RNA-producing genes and 
                  amount of circular RNAs, translational repression of 
                  reporters containing inverted-repeat Alu elements, and 
                  transcriptional rewiring (the creation of mostly nonsensical 
                  novel connections between exons) of susceptible loci. 
                  Biochemical purifications of DHX9 identify the 
                  interferon-inducible isoform of ADAR (p150), but not the 
                  constitutively expressed ADAR isoform (p110), as an 
                  RNA-independent interaction partner. Co-depletion of ADAR 
                  and DHX9 augments the double-stranded RNA accumulation 
                  defects, leading to increased circular RNA production, 
                  revealing a functional link between these two enzymes. Our 
                  work uncovers an evolutionarily conserved function of DHX9. 
                  We propose that it acts as a nuclear RNA resolvase that 
                  neutralizes the immediate threat posed by transposon 
                  insertions and allows these elements to evolve as tools for 
                  the post-transcriptional regulation of gene expression.}
}