In Vivo Mapping of Eukaryotic RNA Interactomes Reveals Principles of Higher-Order Organization and Regulation

Aw, Jong Ghut Ashley; Shen, Yang; Wilm, Andreas; Sun, Miao; Lim, Xin Ni; Boon, Kum-Loong; Tapşın, Sıdıka; Chan, Yun‐Shen; Tan, Cheng-Peow; Sim, Adelene Y. L.; Zhang, Tong; Susanto, Teodorus Theo; Fu, Zhiyan; Nagarajan, Niranjan; Wan, Yao

doi:10.1016/j.molcel.2016.04.028

Cited by 293 publications

(345 citation statements)

References 45 publications

(40 reference statements)

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“…Likewise, a reagent that could distinguish between protections arising from protein binding and those arising from base pairing would yield a quantum advance by providing comprehensive data on base pairing along transcripts and across transcriptomes. Some progress has been made very recently in this direction (3,70,96). Such probes would help determine the extent to which the above-mentioned discrepancies regarding in vivo versus in vitro protections that have arisen in structure-probing studies are the result of protein binding in vivo or of RNA refolding in nonbiological test-tube conditions.…”

Section: Challenges and Future Directionsmentioning

confidence: 99%

Genome-Wide Analysis of RNA Secondary Structure

Bevilacqua¹,

Ritchey²,

et al. 2016

Annu. Rev. Genet.

193

154

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Single-stranded RNA molecules fold into extraordinarily complicated secondary and tertiary structures as a result of intramolecular base pairing. In vivo, these RNA structures are not static. Instead, they are remodeled in response to changes in the prevailing physicochemical environment of the cell and as a result of intermolecular base pairing and interactions with RNAbinding proteins. Remarkable technical advances now allow us to probe RNA secondary structure at single-nucleotide resolution and genome-wide, both in vitro and in vivo. These data sets provide new glimpses into the RNA universe. Analyses of RNA structuromes in HIV, yeast, Arabidopsis, and mammalian cells and tissues have revealed regulatory effects of RNA structure on messenger RNA (mRNA) polyadenylation, splicing, translation, and turnover. Application of new methods for genome-wide identification of mRNA modifications, particularly methylation and pseudouridylation, has shown that the RNA "epitranscriptome" both influences and is influenced by RNA structure. In this review, we describe newly developed genome-wide RNA structure-probing methods and synthesize the information emerging from their application.

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Section: Challenges and Future Directionsmentioning

confidence: 99%

Genome-Wide Analysis of RNA Secondary Structure

Bevilacqua¹,

Ritchey²,

et al. 2016

Annu. Rev. Genet.

193

154

View full text Add to dashboard Cite

show abstract

“…More recently some new methods have been developed to discover the transcriptome-wide RNA interactome that has the potential to cover all RNAs in a cell. These include PARIS (psoralen analysis of RNA interactions and structures) [41,42] (Figure 3A), SPLASH (sequencing of psoralen crosslinked, ligated, and selected hybrids) [43,44] (Figure 3B), LIGR-seq (ligation of interacting Figure 2. Sequencing-based methods to identify RNA-RNA interactions for mediated by a protein or a RNA target.…”

Section: Transcriptome-wide Methodsmentioning

confidence: 99%

“…Some snoRNAs are identified to interact with the helicase Prp43 [77,78]. The authors found many novel snoRNA-rRNA interactions by the Prp43 mutant, suggesting that Prp43 may be another helicase for pre-rRNA releasing from snoRNA [43,77,78]. In Ref.…”

Section: Snorna Related Interactionsmentioning

confidence: 99%

“…Sequencing-based techniques has characterized more and more novel snoRNA-involved RRIs [34,41,43,45]. In Ref.…”

Section: Snorna Related Interactionsmentioning

confidence: 99%

“…For instance, RNA duplexes usually migrate slower in electrophoresis gel, allowing them to be separated from non-interacting RNA fragments [22,23]. Recently, with the advent of next generation sequencing, new techniques based on deep sequencing have been developed to reveal the full network of RRIs, i.e., the interactome, for all transcripts in a cell [41,43,45,46]. They can also be used to study all interactions concerning a certain RNA, usually combined with RNA pull-down with a set of target-specific antisense probes [38,39].…”

Section: Introductionmentioning

confidence: 99%

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Advances and challenges towards the study of RNA-RNA interactions in a transcriptome-wide scale

Gong

Шао

et al. 2018

Quant Biol

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Background: RNA molecules play crucial roles in various biological processes. Their regulation and function are mediated by interacting with other molecules. Among them RNA-RNA interactions (RRIs) are important in many basic cellular activities including transcription, RNA processing, localization, and translation. However, we just start to unveil the complexity of the knowledge and underlying mechanisms of RRIs. Results: In this review, we will summarize approaches for RRI identifications, including both conventional, focused biophysical and biochemical methods and recently developed large scale sequencing-based techniques. We will also discuss discoveries per RRI type revealed by using these technologies, as well as challenges towards a systematic and functional understanding of RRIs. Conclusions: The development of sequencing-based techniques has revolutionized the study of RRIs. Applying these techniques in multiple organisms has identified thousands of RRIs, many of which could potentially regulate multiple aspects of gene expression. However, despite the great breakthrough, the RNA-RNA interactome of any species remains far from complete due to intrinsic complex nature of RRI and limitations in current techniques. More efficient experimental methods and computational framework are needed to obtain the full image of RRI networks, and their possible regulatory roles in biology and medicine.

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The alternative life of RNA—sequencing meets single molecule approaches

Fernández‐Moya¹,

Ehses²,

Kiebler³

2017

FEBS Letters

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The central dogma of RNA processing has started to totter. Single genes produce a variety of mRNA isoforms by mRNA modification, alternative polyadenylation (APA), and splicing. Different isoforms, even those that code for the identical protein, may differ in function or spatiotemporal expression. One option of how this can be achieved is by the selective recruitment of transacting factors to the 3 0 -untranslated region of a given isoform. Recent innovations in high-throughput RNA-sequencing methods allow deep insight into global RNA regulation, whereas novel imaging-based technologies enable researchers to explore single RNA molecules during different stages of development, in different tissues and different compartments of the cell. Resolving the dynamic function of ribonucleoprotein particles in splicing, APA, or RNA modification will enable us to understand their contribution to pathological conditions. Keywords: alternative 3 0 -UTR; local translation; ribonucleoprotein particles Fifteen years ago, the valid explanation of how cells codify and use the information retained in the DNA was very simplistic: genes were transcribed into a unique mRNA, a simple 'messenger' molecule whose only mission was to transfer the information to cytoplasmic ribosomes, so they could be translated into a functional protein. Today, the landscape of the codification, transcription, and translation of our genetic information shows a higher complexity and it is far from being complete. mRNA isoforms: 'modeling' the messageGenic sequences consist of protein-coding sequences (exons) intercalated with sequences (introns) that will be removed by splicing. Inside the nucleus, several steps at either the transcription or the splicing level are involved in modulating the final transcript. Alternative splicing (AS) results in several mRNA isoforms with different exon contributions in its sequence (Fig. 1A.1-3). Under certain circumstances, AS can also produce intron sequence-retaining transcripts that can be exported to the cytoplasm, where they are then degraded via the nonsense-mediated decay (NMD) pathway [1]. However, in certain cases, these intron-retaining transcripts are actually considered post-transcriptional regulatory sequences. Besides AS, the untranslated regions (UTRs) at the 5 0 -and 3 0 -ends of the transcript can alter the function of the messenger and even the coded protein. The UTRs (a) are preferentially targeted by RNA-binding proteins (RBPs), (b) are prone to RNA modifications,

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In Vivo Mapping of Eukaryotic RNA Interactomes Reveals Principles of Higher-Order Organization and Regulation

Cited by 293 publications

References 45 publications

Genome-Wide Analysis of RNA Secondary Structure

Genome-Wide Analysis of RNA Secondary Structure

Advances and challenges towards the study of RNA-RNA interactions in a transcriptome-wide scale

The alternative life of RNA—sequencing meets single molecule approaches

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