title: Transcriptome-wide analysis of regulatory interactions of the RNA-binding protein HuR.
abstract: Posttranscriptional gene regulation relies on hundreds of RNA binding proteins (RBPs) but the function of most RBPs is unknown. The human RBP HuR/ELAVL1 is a conserved mRNA stability regulator. We used PAR-CLIP, a recently developed method based on RNA-protein crosslinking, to identify transcriptome-wide ∼26,000 HuR binding sites. These sites were on average highly conserved, enriched for HuR binding motifs and mainly located in 3' untranslated regions. Surprisingly, many sites were intronic, implicating HuR in mRNA processing. Upon HuR knockdown, mRNA levels and protein synthesis of thousands of target genes were downregulated, validating functionality. HuR and miRNA binding sites tended to reside nearby but generally did not overlap. Additionally, HuR knockdown triggered strong and specific upregulation of miR-7. In summary, we identified thousands of direct and functional HuR targets, found a human miRNA controlled by HuR, and propose a role for HuR in splicing.
authors: Laboratory of Systems Biology of Gene Regulatory Elements, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors: Svetlana
authors: S
authors: Lebedeva
authors: Marvin
authors: M
authors: Jens
authors: Kathrin
authors: K
authors: Theil
authors: Björn
authors: B
authors: Schwanhäusser
authors: Matthias
authors: M
authors: Selbach
authors: Markus
authors: M
authors: Landthaler
authors: Nikolaus
authors: N
authors: Rajewsky
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA
chemical_list: D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins