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Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals virus-snoRNA interactions

ABSTRACT: Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals virus-snoRNA interactions

PROVIDER: PRJNA692757 | ENA |

REPOSITORIES: ENA

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			Action	DRS
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	SRR13451200.fastq.gz	Fastqsanger.gz
	SRR13451201.fastq.gz	Fastqsanger.gz
	SRR13451202.fastq.gz	Fastqsanger.gz
	SRR13451203.fastq.gz	Fastqsanger.gz

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Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals virus-snoRNA interactions

Project description:SARS-CoV-2 coronavirus is one of the largest RNA viruses (26-32kb) and has emerged as a major threat to global public health. The resulting pandemic has caused global societal and economic disruptions. Here, we investigate the intramolecular and intermolecular RNA interactions of wildtype and a 382 deletion SARS-CoV-2 virus inside cells. We identified twelve potentially functional structural elements along the SARS-CoV-2 genome and observed that subgenomic viral RNA (sgRNAs) contains different structures that could be important for their functions using direct RNA sequencing. Proximity ligation sequencing experiments identified hundreds of intramolecular and intermolecular pair-wise interactions within the virus genome and between virus and host cellular RNAs. SARS-CoV-2 binds strongly to mitochondrial and nucleolar RNAs including COX1 and SNORD27, and contains 130 2’O-methylation sites along its genome. 2’O-methylation sites along the virus RNA are enriched in the UTRs and associated with increased pair-wise interactions. SARS-CoV-2 infection also results in a global decrease of 2’O-methylation sites on host mRNAs, suggesting that binding of SARS-CoV-2 to snoRNAs could be a pro-viral mechanism to sequester methylation machinery away from host RNAs to methylate the virus genome. Collectively, these studies deepen our understanding of the molecular basis of SARS-CoV-2 pathogenicity, its cellular host factors and provides a platform for targeting the virus.

2021-07-05 | GSE165005 | GEO

Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions.

Project description:SARS-CoV-2 is a major threat to global health. Here, we investigate the RNA structure and RNA-RNA interactions of wildtype (WT) and a mutant (Δ382) SARS-CoV-2 in cells using Illumina and Nanopore platforms. We identify twelve potentially functional structural elements within the SARS-CoV-2 genome, observe that subgenomic RNAs can form different structures, and that WT and Δ382 virus genomes fold differently. Proximity ligation sequencing identify hundreds of RNA-RNA interactions within the virus genome and between the virus and host RNAs. SARS-CoV-2 genome binds strongly to mitochondrial and small nucleolar RNAs and is extensively 2'-O-methylated. 2'-O-methylation sites are enriched in viral untranslated regions, associated with increased virus pair-wise interactions, and are decreased in host mRNAs upon virus infection, suggesting that the virus sequesters methylation machinery from host RNAs towards its genome. These studies deepen our understanding of the molecular and cellular basis of SARS-CoV-2 pathogenicity and provide a platform for targeted therapy.

| S-EPMC8387478 | biostudies-literature

SnoRNA-facilitated protein secretion revealed by transcriptome-wide snoRNA target identification

Project description:Small nucleolar RNAs (snoRNA) are non-coding RNAs known for guiding RNA modifications including 2ʹ-O-methylation (Nm) and pseudouridine (Ψ). While snoRNAs may also interact with other RNAs such as mRNA, the full repertoire of RNAs targeted by snoRNA remains elusive due to the lack of effective technologies that identify snoRNA targets transcriptome-wide. Here we develop a chemical crosslinking-based approach that comprehensively detects cellular RNA targets of snoRNAs, yielding thousands of previously unrecognized snoRNA-mRNA interactions in human cells and mouse brain tissues. Many interactions occur outside of snoRNA-guided rRNA modification sites, hinting at non-canonical functions beyond RNA modification. We find that one of these snoRNAs, SNORA73, targets mRNAs that encode secretory proteins and membrane proteins. SNORA73 also interacts with 7SL RNA, part of the signal recognition particle (SRP) required for protein secretion. The mRNA-SNORA73-7SL RNA interactions enhance the association of the SNORA73-target mRNAs with SRP, thereby facilitating secretion of the encoded proteins.

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Mapping snoRNA-target RNA interactions in an RNA binding protein-dependent manner with chimeric eCLIP [eCLIP]

Project description:To identify the snoRNAs, we perfromed eCLIP with all snoRNA binding proteins as baits.

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Mapping snoRNA-target RNA interactions in an RNA binding protein-dependent manner with chimeric eCLIP [Ribo_Meth-seq]

Project description:To determine potential snoRNA-guided methylation in rRNA and snRNA in mESC, we performed RiboMeth-seq to quantify 2'-O-methylation levels.

2025-01-16 | GSE277419 | GEO

Mapping snoRNA-target RNA interactions in an RNA binding protein-dependent manner with chimeric eCLIP [chimeric eCLIP]

Project description:To indentify the targets of snoRNAs, we adapted an enhanced chimeric eCLIP approach,utilizing both established core proteins and lesser-known snoRNA-associated RBPs as bait. .

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Project description:Box C/D small nucleolar RNAs (snoRNAs) are a conserved class of RNA known for their role in guiding ribosomal RNA 2’-O-ribose methylation through base pairing with targeted sequences. Recently, C/D snoRNAs were also implicated in regulating the expression of non-ribosomal genes through different modes of binding. Large scale RNA-RNA interaction datasets detect many snoRNAs binding messenger RNA. However, these studies provide a narrow portrait of snoRNA targets forming under specific experimental conditions. To enable a more comprehensive study of C/D snoRNA interactions, we created snoGloBe, a human C/D snoRNA machine learning interaction predictor based on a gradient boosting classifier. SnoGloBe considers the target type, and position and sequence of the interactions, enabling it to outperform existing predictors. Interestingly, for specific snoRNAs, snoGloBe identifies strong enrichment of interactions near gene expression regulatory elements including splice sites. Abundance and splicing of predicted targets were altered upon the knockdown of their associated snoRNA. Strikingly, the predicted snoRNA interactions often overlap with the binding sites of functionally related RNA binding proteins, reinforcing their role in gene expression regulation. The interactions of snoRNAs are not randomly distributed but often accumulate in functionally related transcripts sharing common regulatory elements suggesting coordinated regulatory function. The wide scope of snoGloBe makes it an excellent tool for discovering viral RNA targets, which is evident from its capacity to identify snoRNAs targeting SARS-CoV-2 RNA, known to be heavily methylated. Overall, snoGloBe is capable of identifying experimentally validated binding sites and predicting novel sites with shared regulatory function.

2022-05-18 | GSE184173 | GEO

Global Mapping of Human RNA-RNA Interactions

Project description:We describe a new method enabling the global-scale mapping of RNA-RNA duplexes cross-linked in vivo, ‘LIGation of interacting RNA followed by high-throughput Sequencing’ (LIGR-Seq). Applying this method in human cells reveals a remarkable landscape of new RNA-RNA interactions involving all major classes of ncRNA, and mRNA. LIGR-Seq data reveal unexpected interactions between small nucleolar (sno)RNAs and mRNAs, including interactions involving the orphan C/D box snoRNA, SNORD83B, that control steady-state levels of its target mRNAs. LIGR-Seq thus represents a powerful approach for illuminating the functions of the myriad of uncharacterized RNAs that act via base-pairing interactions.

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Mapping snoRNA-target RNA interactions in an RNA binding protein-dependent manner with chimeric eCLIP [eCLIP]

Project description:Mapping snoRNA-target RNA interactions in an RNA binding protein-dependent manner with chimeric eCLIP [eCLIP]

| PRJNA1162138 | ENA

A microRNA and snoRNA expression profile in the synchronous colorectal cancer

Project description:We evaluated the profile of miRNA and snoRNA expression in 5 synchronous CRC and matched normal colorectal tissues using the Affymetrix GeneChip miRNA 1.0 array. A total of 24 miRNA differential expressed transcripts which represent 27 mature miRNAs, including an oncogenic miR-17-92a and oncosuppressive miR-143-145 cluster, and a global up-regulation of snoRNAs were revealed in cancer tissues compared with matched normal tissues. Global miRNA expression could distinguish synchronous cancer from normal mucosa. Our findings represent the first comprehensive miRNA and snoRNA expression signatures for synchronous CRC, which increase the understanding of the molecular basis of synchronous CRC, and firstly implicate that dysregulation of snoRNAs and miRNA clusters may present therapeutic targets for synchronous CRC. Examination of microRNA and snoRNA expression in synchronous CRC and matched normal colorectal tissues

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