RNA duplex map in living cells reveals higher order transcriptome structure

By Zhipeng Lu, Qiangfeng Cliff Zhang, Byron Lee, Ryan A. Flynn, Martin A. Smith, James T. Robinson, C. Davidovich, A. Gooding, Karen J. Goodrich, John S. Mattick and 3 more. 2016

569 citations recorded by the source corpus.

SUMMARY 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 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.

Subfields: Cancer Research, Molecular Biology

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In Molecular Biology

1. Benjamin J. Blencowe
2. Lothar Schermelleh
3. N. Brockdorff
4. T. Nesterova
5. A. Ren
6. Jernej Ule

Citations in the corpus

• Recent advances in RNA structurome (2022, methodology): “Meanwhile, RNA proximity ligation-based highthroughput profiling methods have been developed to identify genome-wide RNA-RNA interactions, such as psoralen analysis of RNA interactions and structures (PARIS) (Lu et al., 2016) and RNA in situ conformation sequencing (RICseq) technology (Cai et al., 2”
• Alternative Splicing Regulatory Networks: Functions, Mechanisms, and Evolution. (2019, methodology): “Similarly, methods for the transcriptome-wide mapping of spliceosomal assembly and RNARNA contacts, including both intra- and inter-molecular contacts, will be important for understanding how RNA structures regulate the formation of functional RNP complexes and the availability of splice sites or th”
• Time-resolved structured illumination microscopy reveals key principles of Xist RNA spreading (2020, methodology): “The protein SPEN, which binds to the Arepeat region of Xist RNA through a triple RRM domain, plays a central role in Xistmediated gene silencing (8, 17, 22, 23).”