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In vivo atlas of RNA secondary structures recognized by ADARs

ABSTRACT: In vivo atlas of RNA secondary structures recognized by ADARs

PROVIDER: PRJNA562274 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10022345.fastq.gz	Fastqsanger.gz
	SRR10022346.fastq.gz	Fastqsanger.gz
	SRR10022347.fastq.gz	Fastqsanger.gz
	SRR10022348.fastq.gz	Fastqsanger.gz
	SRR10022349.fastq.gz	Fastqsanger.gz

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In vivo atlas of RNA secondary structures recognized by ADARs [RNA-Seq]

Project description:In vivo atlas of RNA secondary structures recognized by ADARs [RNA-Seq]

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In vivo atlas of RNA secondary structures recognized by ADARs

Project description:This SuperSeries is composed of the SubSeries listed below.

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In vivo atlas of RNA secondary structures recognized by ADARs [RNA-Seq]

Project description:We performed irCLASH and HiCLIP for ADAR1-3 in HEK293 cells. In addition, we performed mRNA-seq in ADAR1-3 overexpressed HEK293 cells and control HEK293 cells

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In vivo atlas of RNA secondary structures recognized by ADARs [irCLASH-seq&hiCLIP-seq]

Project description:We performed irCLASH and HiCLIP for ADAR1-3 in HEK293 cells. In addition, we performed mRNA-seq in ADAR1-3 overexpressed HEK293 cells and control HEK293 cells

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ADARs regulate small RNAs mapped to edited sequences

Project description:Cellular RNAs containing double-stranded RNA (dsRNA) structures are subject to A-to-I RNA editing by the adenosine deaminases that act on RNA (ADARs). While A-to-I editing can alter mRNA coding potential, most editing is observed in non-coding sequences, the function of which remains poorly characterized. To correlate small RNA population with expression patterns of ADARs and hyperedited RNAs (editing-enriched regions: EERs) defined and characterized in a separate RNAseq analysis, we re-analyzed existing smallRNAseq datasets of a wildtype strain and a strain lacking ADARs (adr-1;adr-2). Analysis of primary siRNAs from mixed-stage worms revealed that ADARs impact siRNA biogenesis from EERs. We then analyzed primary and secondary RNAs mapping to EERs from embryo-stage or L4-stage worms and observed that ADAR effects on siRNA levels are dependent on developmental stage.

2018-02-23 | GSE89765 | GEO

ADARs act as potent regulators of circular transcriptome in cancer

Project description:Circular RNAs (circRNAs) are produced by head-to-tail back-splicing which is mainly facilitated by base-pairing of reverse complementary matches (RCMs) in circRNA flanking introns. Adenosine deaminases acting on RNA (ADARs) are known to bind double-stranded RNAs for adenosine to inosine (A-to-I) RNA editing. Here we characterize ADARs as potent regulators of circular transcriptome by identifying over a thousand of circRNAs regulated by ADARs in a bidirectional manner through and beyond their editing function. We found that editing can stabilize or destabilize secondary structures formed between RCMs via correcting A:C mismatches to I(G)-C pairs or creating I(G).U wobble pairs, respectively. We provided experimental evidence that editing also favors the binding of RNA-binding proteins such as PTBP1 to regulate back-splicing. These ADARs-regulated circRNAs which are ubiquitously expressed in multiple types of cancers, demonstrate high functional relevance to cancer. Our findings support a hitherto unappreciated bidirectional regulation of circular transcriptome by ADARs and highlights the complexity of cross-talk in RNA processing and its contributions to tumorigenesis.

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

Project description: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.

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Project description:Adenosine deaminases that act on RNA (ADARs) catalyze the conversion of adenosine to inosine in dsRNA. C. elegans ADARs, ADR-1 and ADR-2, promote the expression of genes containing dsRNA structures by preventing their processing into siRNAs and silencing by RNAi. The 26G endogenous siRNA (endo-siRNA) pathway generates a subset of siRNAs distinct from those made in adr-1;adr-2 mutants, but using many of the same factors. We found that adr-1;adr-2;rrf-3 mutants, lacking both ADARs and the RNA-dependent RNA polymerase RRF-3 required for the 26G pathway, display a bursting phenotype rescued by the RNAi factors RDE-1 and RDE-4. To determine what gene expression changes underlie the synthetic phenotype of adr-1;adr-2;rrf-3 mutants, we sequenced poly(A)+ RNA from adr-1;adr-2;rrf-3 embryos, their parent strains, and strains rescued with mutations in rde-1 and rde-4. We found that genes associated with edited structures were robustly downregulated in adr-1;adr-2;rrf-3 mutants in a manner partially dependent on rde-1 and rde-4. Additionally, genes induced during Orsay virus infections were induced in rrf-3 mutants and further upregulated in adr-1;adr-2;rrf-3 mutants, again dependent in part on rde-1 and rde-4.

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Genome-wide profiling of mouse RNA secondary structures reveals key features of the mammalian transcriptome

Project description:By using a novel high-throughput method, named chemical inference of RNA structures (CIRS-seq), that uses dimethyl sulfate (DMS), and N-cyclohexyl-N'-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate (CMCT) to modify RNA residues in single-stranded conformation within native RNA secondary structures, we investigated the structural features of mouse embryonic stem cell (ESC) transcripts. Our analysis revealed an unexpected higher structuring of the 5' and 3' untranslated regions (UTRs) compared to the coding regions, a reduced structuring at the Kozak sequence and stop codon, and a three-nucleotide periodicity across the coding region of messenger RNAs. We also observed that ncRNAs exhibit a higher degree of structuring with respect to protein coding transcripts. Moreover, we found that the Lin28a binding protein binds selectively to RNA motifs with a strong preference toward a single stranded conformation. Transcritome-wide mapping of RNA secondary structures in mouse embryonic stem cells (mESC)

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