title: hiCLIP reveals the in vivo atlas of mRNA secondary structures recognized by Staufen 1.
abstract: The structure of messenger RNA is important for post-transcriptional regulation, mainly because it affects binding of trans-acting factors. However, little is known about the in vivo structure of full-length mRNAs. Here we present hiCLIP, a biochemical technique for transcriptome-wide identification of RNA secondary structures interacting with RNA-binding proteins (RBPs). Using this technique to investigate RNA structures bound by Staufen 1 (STAU1) in human cells, we uncover a dominance of intra-molecular RNA duplexes, a depletion of duplexes from coding regions of highly translated mRNAs, an unexpected prevalence of long-range duplexes in 3' untranslated regions (UTRs), and a decreased incidence of single nucleotide polymorphisms in duplex-forming regions. We also discover a duplex spanning 858 nucleotides in the 3' UTR of the X-box binding protein 1 (XBP1) mRNA that regulates its cytoplasmic splicing and stability. Our study reveals the fundamental role of mRNA secondary structures in gene expression and introduces hiCLIP as a widely applicable method for discovering new, especially long-range, RNA duplexes.
authors: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
authors: Yoichiro
authors: Y
authors: Sugimoto
authors: 1] Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK [2] UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, Gower Street, London WC1E 6BT, UK.
authors: Alessandra
authors: A
authors: Vigilante
authors: Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors: Elodie
authors: E
authors: Darbo
authors: Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors: Alexandra
authors: A
authors: Zirra
authors: Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors: Cristina
authors: C
authors: Militti
authors: 1] MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK [2] Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors: Andrea
authors: A
authors: D'Ambrogio
authors: 1] Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK [2] UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, Gower Street, London WC1E 6BT, UK [3] Okinawa Institute of Science &Technology, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa 904-0495, Japan.
authors: Nicholas M
authors: NM
authors: Luscombe
authors: 1] MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK [2] Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors: Jernej
authors: J
authors: Ule
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D009690:Nucleic Acid Conformation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012326:RNA Splicing; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000235:genetics; D000071717:X-Box Binding Protein 1
chemical_list: D020413:3' Untranslated Regions; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; C492185:STAU1 protein, human; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human