title: RNA Duplex Map in Living Cells Reveals Higher-Order Transcriptome Structure.
abstract: RNA has the intrinsic property to base pair, forming complex structures fundamental to its diverse functions. Here, we develop PARIS, a method based on reversible psoralen crosslinking for global mapping of RNA duplexes with near base-pair resolution in living cells. PARIS analysis in three human and mouse cell types reveals frequent long-range structures, higher-order architectures, and RNA-RNA interactions in trans across the transcriptome. PARIS determines base-pairing interactions on an individual-molecule level, revealing pervasive alternative conformations. We used PARIS-determined helices to guide phylogenetic analysis of RNA structures and discovered conserved long-range and alternative structures. XIST, a long noncoding RNA (lncRNA) essential for X chromosome inactivation, folds into evolutionarily conserved RNA structural domains that span many kilobases. XIST A-repeat forms complex inter-repeat duplexes that nucleate higher-order assembly of the key epigenetic silencing protein SPEN. PARIS is a generally applicable and versatile method that provides novel insights into the RNA structurome and interactome. VIDEO ABSTRACT.
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA; MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology, Center for Synthetic and Systems Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Qiangfeng Cliff
authors.initials: QC
authors.lastname: Zhang
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
authors.forename: Byron
authors.initials: B
authors.lastname: Lee
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Flynn
authors.affiliation: RNA Biology and Plasticity Group, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, UNSW Medicine, NSW 2052, Australia.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Smith
authors.affiliation: Department of Medicine and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Robinson
authors.affiliation: HHMI and Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80303, USA; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Victoria 3800, Australia; EMBL Australia and the ARC Centre of Excellence in Advanced Molecular Imaging, Clayton, VIC 3800, Australia.
authors.forename: Chen
authors.initials: C
authors.lastname: Davidovich
authors.affiliation: HHMI and Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80303, USA.
authors.forename: Anne R
authors.initials: AR
authors.lastname: Gooding
authors.affiliation: HHMI and Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80303, USA.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Goodrich
authors.affiliation: RNA Biology and Plasticity Group, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, UNSW Medicine, NSW 2052, Australia.
authors.forename: John S
authors.initials: JS
authors.lastname: Mattick
authors.affiliation: Department of Medicine and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Jill P
authors.initials: JP
authors.lastname: Mesirov
authors.affiliation: HHMI and Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80303, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Cech
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA. Electronic address: howchang@stanford.edu.
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
mesh_terms: D000818:Animals; D020029:Base Pairing; D005363:Ficusin / Q000737:chemistry*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D000066450:Mouse Embryonic Stem Cells; D012330:RNA, Double-Stranded / Q000737:chemistry*; D062085:RNA, Long Noncoding / Q000737:chemistry
chemical_list: D012330:RNA, Double-Stranded; D062085:RNA, Long Noncoding; C077885:XIST non-coding RNA; D005363:Ficusin