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

Item Type:Article
Title:hiCLIP reveals the in vivo atlas of mRNA secondary structures recognized by Staufen 1
Creators Name:Sugimoto, Y. and Vigilante, A. and Darbo, E. and Zirra, A. and Militti, C. and D'Ambrogio, A. and Luscombe, N.M. and Ule, J.
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.
Keywords:3' Untranslated Regions, Base Sequence, Cytoplasm, Cytoskeletal Proteins, DNA-Binding Proteins, Messenger RNA, Nucleic Acid Conformation, RNA Splicing, RNA Stability, RNA-Binding Proteins, Regulatory Factor X Transcription Factors, Single Nucleotide Polymorphism, Transcription Factors, X-Box Binding Protein 1
Publisher:Nature Publishing Group
Page Range:491-494
Date:26 March 2015
Official Publication:https://doi.org/10.1038/nature14280
PubMed:View item in PubMed

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