Journal
NATURE
Volume 519, Issue 7544, Pages 491-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/nature14280
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Categories
Funding
- Human Frontier Science Program [RGP0024/2008-C]
- European Research Council [206726-CLIP, 617837-Translate]
- Medical Research Council [U105185858]
- Cancer Research UK
- UCL
- Wellcome Trust [103760/Z/14/Z]
- Nakajima Foundation
- MRC
- Cancer Research UK [16358] Funding Source: researchfish
- Medical Research Council [MC_U105185858] Funding Source: researchfish
- The Francis Crick Institute [10111, 10110] Funding Source: researchfish
- Wellcome Trust [103760/Z/14/Z] Funding Source: researchfish
- MRC [MC_U105185858] Funding Source: UKRI
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The structure of messenger RNA is important for post-transcriptional regulation, mainly because it affects binding of trans-acting factors(1). 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 39 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 39 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 introduce shiCLIPas a widely applicable method for discovering new, especially long-range, RNA duplexes.
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