title: Transposable elements modulate human RNA abundance and splicing via specific RNA-protein interactions.
abstract: BACKGROUND
  Transposable elements (TEs) have significantly influenced the evolution of transcriptional regulatory networks in the human genome. Post-transcriptional regulation of human genes by TE-derived sequences has been observed in specific contexts, but has yet to be systematically and comprehensively investigated. Here, we study a collection of 75 CLIP-Seq experiments mapping the RNA binding sites for a diverse set of 51 human proteins to explore the role of TEs in post-transcriptional regulation of human mRNAs and lncRNAs via RNA-protein interactions.
  
  
  RESULTS
  We detect widespread interactions between RNA binding proteins (RBPs) and many families of TE-derived sequence in the CLIP-Seq data. Further, alignment coverage peaks on specific positions of the TE consensus sequences, illuminating a diversity of TE-specific RBP binding motifs. Evidence of binding and conservation of these motifs in the nonrepetitive transcriptome suggests that TEs have generally appropriated existing sequence preferences of the RBPs. Depletion assays for numerous RBPs show that TE-derived binding sites affect transcript abundance and splicing similarly to nonrepetitive sites. However, in a few cases the effect of RBP binding depends on the specific TE family bound; for example, the ubiquitously expressed RBP HuR confers transcript stability unless bound to an Alu element.
  
  
  CONCLUSIONS
  Our meta-analysis suggests a widespread role for TEs in shaping RNA-protein regulatory networks in the human genome.
authors.forename: David R
authors.initials: DR
authors.lastname: Kelley
authors.forename: David G
authors.initials: DG
authors.lastname: Hendrickson
authors.forename: Danielle
authors.initials: D
authors.lastname: Tenen
authors.forename: John L
authors.initials: JL
authors.lastname: Rinn
mesh_terms: D001665:Binding Sites; D004251:DNA Transposable Elements; D053263:Gene Regulatory Networks; D006801:Humans; D020014:K562 Cells; D008969:Molecular Sequence Data; D012313:RNA / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements; D016601:RNA-Binding Proteins; D012313:RNA