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Nature. 2015 Mar 26;519(7544):491-4. doi: 10.1038/nature14280. Epub 2015 Mar 18.

hiCLIP reveals the in vivo atlas of mRNA secondary structures recognized by Staufen 1.

Author information

1
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
2
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
Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
4
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
5
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.
6
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.

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.

Comment in

PMID:
25799984
PMCID:
PMC4376666
DOI:
10.1038/nature14280
[Indexed for MEDLINE]
Free PMC Article

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