RIC-seq for global in situ profiling of RNA–RNA spatial interactions

Cai, Zi; Cao, Changchang; Ji, Lei; Ye, Rong; Wang, Di; Xia, Cong; Wang, Sui; Du, Zongchang; Hu, Naijing; Yu, Xiaohua; Chen, Juan; Wang, Lei; Yang, Xianguang; He, Shunmin; Xue, Yuanchao

doi:10.1038/s41586-020-2249-1

Cited by 222 publications

(249 citation statements)

References 57 publications

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“…A recent study reported a novel method, RNA in situ conformation sequencing (RIC) technology, for the global mapping of intra-and intermolecular RNA-RNA interactions ( Fig. 5) [80]. Compared to the RNA ligation induced in vitro in previous methods, RIC-seq performs RNA proximity ligation in situ, and it enriches chimeric reads using a biotinylated cytidine phosphate (pCp-biotin) [80].…”

Section: Rna-rna Spatial Interactionsmentioning

confidence: 99%

Principles and innovative technologies for decrypting noncoding RNAs: from discovery and functional prediction to clinical application

Sun

Chen

2020

J Hematol Oncol

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Noncoding RNAs (ncRNAs) are a large segment of the transcriptome that do not have apparent protein-coding roles, but they have been verified to play important roles in diverse biological processes, including disease pathogenesis. With the development of innovative technologies, an increasing number of novel ncRNAs have been uncovered; information about their prominent tissue-specific expression patterns, various interaction networks, and subcellular locations will undoubtedly enhance our understanding of their potential functions. Here, we summarized the principles and innovative methods for identifications of novel ncRNAs that have potential functional roles in cancer biology. Moreover, this review also provides alternative ncRNA databases based on highthroughput sequencing or experimental validation, and it briefly describes the current strategy for the clinical translation of cancer-associated ncRNAs to be used in diagnosis.

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Section: Rna-rna Spatial Interactionsmentioning

confidence: 99%

Principles and innovative technologies for decrypting noncoding RNAs: from discovery and functional prediction to clinical application

Sun

Chen

2020

J Hematol Oncol

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“…Using the MS2-tethering approach histone H2b RNA was found capable to induce subnuclear structures resembling histone locus bodies and RNA from a β-globin minigene to assemble splicing speckle components into nuclear puncta (Shevtsov and Dundr, 2011). Chromosome conformation techniques and proximity mapping of pairwise or multiple RNAs simultaneously (Lieberman-Aiden et al, 2009;Morf et al, 2019;Cai et al, 2020) in combination with measurements of transcription output and kinetics might be one way to comprehensively identify regulatory relationships between transcripts and genes. Furthermore, recent advances that allow monitoring of genome architecture and transcription at the single-cell level (Nagano et al, 2013;Stevens et al, 2017;Larsson et al, 2019) will provide further insights into how the interplay between genome structure, RNA, and characteristics of its synthesis, regulates proximal gene transcription with high spatial specificity.…”

Section: Discussionmentioning

confidence: 99%

RNA, Genome Output and Input

2020

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RNA, the transcriptional output of genomes, not only templates protein synthesis or directly engages in catalytic functions, but can feed back to the genome and serve as regulatory input for gene expression. Transcripts affecting the RNA abundance of other genes act by mechanisms similar to and in concert with protein factors that control transcription. Through recruitment or blocking of activating and silencing complexes to specific genomic loci, RNA and protein factors can favor transcription or lower the local gene expression potential. Most regulatory proteins enter nuclei from all directions to start the search for increased affinity to specific DNA sequences or to other proteins nearby genuine gene targets. In contrast, RNAs emerge from spatial point sources within nuclei, their encoding genes. A transcriptional burst can result in the local appearance of multiple nascent RNA copies at once, in turn increasing local nucleic acid density and RNA motif abundance before diffusion into the nuclear neighborhood. The confined initial localization of regulatory RNAs causing accumulation of protein co-factors raises the intriguing possibility that target specificity of non-coding, and probably coding, RNAs is achieved through gene/RNA positioning and spatial proximity to regulated genomic regions. Here we review examples of positional cis conservation of regulatory RNAs with respect to target genes, spatial proximity of enhancer RNAs to promoters through DNA looping and RNA-mediated formation of membrane-less structures to control chromatin structure and expression. We speculate that linear and spatial proximity between regulatory RNA-encoding genes and gene targets could possibly ease the evolutionary pressure on maintaining regulatory RNA sequence conservation.

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“…Given that the RS splicing machinery utilizes a specific AGGT site while ignoring others (Duff et al, 2015;Hayashi et al, 2018;Joseph et al, 2018;Pai et al, 2018;Sibley et al, 2016;Sibley et al, 2015;Zhang et al, 2018), the RS sites may carry unique features compared to the non-RS AGGT sites. We found that RS sites exhibit specific primary sequence context of U1 snRNA binding site and polypyrimidine tract, which may recruit RNA binding proteins (RBPs), such as exon junction complex and polypyrimidine tract binding proteins (Blazquez et al, 2018;Cai et al, 2020;Duff et al, 2015;Patton et al, 2020;Ule and Blencowe, 2019;Van Nostrand et al, 2020;Xue et al, 2009), to facilitate the recognition of 3'SS. Thus, profiling RBP bindings and RNA structures around the RS and non-RS AGGT sites are necessary to further illustrate the molecular basis of RS.…”

Section: Discussionmentioning

confidence: 99%

Recursive splicing is a rare event in the mouse brain

Moon

Zhao

2020

Preprint

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SummaryRecursive splicing (RS) is a mechanism to excise long introns from messenger RNA precursors. We focused on nuclear RNA, which is enriched for RS splicing intermediates and nascent transcripts, to investigate RS in the mouse brain. We identified new RS sites and discovered that RS is constitutive between excitatory and inhibitory neurons and between sexes in the mouse cerebral cortex. Moreover, we found that the primary sequence context, including the U1 snRNA binding site, the polypyrimidine tract, and a strong 3’ splice site, determines RS sites in long introns. We also uncovered a new type of exon-like RS events termed exonicRS that may represent an intermediate stage of RS sites evolving into annotated exons. Furthermore, the strengths of 5’ splice sites are able to classify RS events into RS sites and exonicRS. Overall, these findings provide mechanistic insights into the splicing and evolution of long genes.

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RIC-seq for global in situ profiling of RNA–RNA spatial interactions

Cited by 222 publications

References 57 publications

Principles and innovative technologies for decrypting noncoding RNAs: from discovery and functional prediction to clinical application

Principles and innovative technologies for decrypting noncoding RNAs: from discovery and functional prediction to clinical application

RNA, Genome Output and Input

Recursive splicing is a rare event in the mouse brain

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