hiCLIP reveals the in vivo atlas of mRNA secondary structures recognized by Staufen 1
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Yoichiro Sugimoto Alessandra Vigilante Elodie Darbo Alexandra Zirra Cristina Militti Andrea D'Ambrogio Nicholas Luscombe Jernej UleAbstract
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.
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Journal Nature
Volume 519
Issue number 7544
Pages 491-494
Available online
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Publisher website (DOI) 10.1038/nature14280
Europe PubMed Central 25799984
Pubmed 25799984
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