Publication Date:
2015-03-25
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376666/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376666/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sugimoto, Yoichiro -- Vigilante, Alessandra -- Darbo, Elodie -- Zirra, Alexandra -- Militti, Cristina -- D'Ambrogio, Andrea -- Luscombe, Nicholas M -- Ule, Jernej -- 103760/Wellcome Trust/United Kingdom -- 103760/Z/14/Z/Wellcome Trust/United Kingdom -- 206726/European Research Council/International -- 617837/European Research Council/International -- A16358/Cancer Research UK/United Kingdom -- MC_U105185858/Medical Research Council/United Kingdom -- U105185858/Medical Research Council/United Kingdom -- England -- Nature. 2015 Mar 26;519(7544):491-4. doi: 10.1038/nature14280. Epub 2015 Mar 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; 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. ; Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK. ; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. ; 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. ; 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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25799984" target="_blank"〉PubMed〈/a〉
Keywords:
3' Untranslated Regions/genetics
;
Base Sequence
;
Cytoplasm/genetics/metabolism
;
Cytoskeletal Proteins/*metabolism
;
DNA-Binding Proteins/genetics
;
Humans
;
*Nucleic Acid Conformation
;
Polymorphism, Single Nucleotide/genetics
;
RNA Splicing
;
RNA Stability
;
RNA, Messenger/*chemistry/genetics/*metabolism
;
RNA-Binding Proteins/*metabolism
;
Transcription Factors/genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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