Human ANGIOGENIN is sufficient but not required for tRNA cleavage to generate tRNA fragments
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA541296 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9018490.fastq.gz | Fastqsanger.gz | |||
| SRR9018500.fastq.gz | Fastqsanger.gz | |||
| SRR9018491.fastq.gz | Fastqsanger.gz | |||
| SRR9018501.fastq.gz | Fastqsanger.gz | |||
| SRR9018492.fastq.gz | Fastqsanger.gz |
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Project description:To identify tRNA fragments regulated by angiogenin (ANG, Rnase 5), we sequenced 15-50nt small RNAs upon ANG overexpression and ANG knockout.
2019-10-01 | GSE130764 | GEO
Project description:Angiogenin is a stress-activated ribonuclease that cleaves tRNA within anticodon loops to produce tRNA-derived stress-induced fragments (tiRNAs). Transfection of natural or synthetic tiRNAs inhibits protein synthesis and triggers the phospho-eIF2?-independent assembly of stress granules (SGs), essential components of the stress response program. We show that selected tiRNAs inhibit protein synthesis by displacing eIF4G/eIF4A from uncapped > capped RNAs. tiRNAs also displace eIF4F, but not eIF4E:4EBP1, from isolated m(7)G cap. We identify a terminal oligoguanine motif that is required to displace the eIF4F complex, inhibit translation, and induce SG assembly. We show that the tiRNA-associated translational silencer YB-1 contributes to angiogenin-, tiRNA-, and oxidative stress-induced translational repression. Our data reveal some of the mechanisms by which stress-induced tRNA cleavage inhibits protein synthesis and activates a cytoprotective stress response program.
| S-EPMC3160621 | biostudies-literature
Project description:Specific environmental insults cause the limited fragmentation of transfer RNAs (tRNAs) into tRNA-derived small RNAs (tsRNAs), which have been implicated in a wide range of biological processes. tRNA fragmentation results from endonucleolytic activities targeting single-stranded tRNA regions. However, how a tRNA with a single hydrolyzed phosphodiester bond in the anticodon loop (‘nicked’ tRNA) gives rise to distinct tsRNAs remains poorly understood. After identifying RNA helicases that were able to unwind ‘nicked’ tRNAs in vitro, the specificity of one of those enzymes, DDX3X, was determined by RNA helicase assays on tRNAs, which had been subjected to recombinant Angiogenin. Both in vivo ‘nicked’ tRNAs, DDX3X-unwound ‘nicked’ tRNAs as well as heat-denatured ‘nicked’ tRNAs were subjected to small RNA sequencing.
2022-04-05 | GSE187021 | GEO
Project description:In this review, we summarise the evidence for a role of the ribonuclease angiogenin in the pathophysiology of neurodegenerative disorders, with a specific focus on Parkinson's disease (PD). Angiogenin is a stress-induced, secreted ribonuclease with both nuclear and cytosolic activities. Loss-of-function mutations in the angiogenin gene (ANG) have been initially discovered in familial cases of amyotrophic lateral sclerosis (ALS), however, variants in ANG have subsequently been identified in PD and Alzheimer's disease. Delivery of angiogenin protein reduces neurodegeneration and delays disease progression in in vitro and in vivo models of ALS and in vitro models of PD. In the nucleus, angiogenin promotes ribosomal RNA transcription. Under stress conditions, angiogenin also translocates to the cytosol where it cleaves non-coding RNA into RNA fragments, in particular transfer RNAs (tRNAs). Stress-induced tRNA fragments have been proposed to have multiple cellular functions, including inhibition of ribosome biogenesis, inhibition of protein translation and inhibition of apoptosis. We will discuss recent evidence of tRNA fragment accumulation in PD, as well as their potential neuroprotective activities.
| S-EPMC7470775 | biostudies-literature
Project description:Mutations in the cytosine-5 RNA methyltransferase NSun2 can cause Intellectual Disability (ID) and symptoms commonly found in patients with Dubowitz syndrome. By analysing gene expression data with the global cytosine-5 RNA methylome in NSun2-deficient mice, we find that loss of cytosine-5 RNA methylation increases the fragmentation of transfer RNAs (tRNA) leading to an accumulation of 5M-bM-^@M-^Y halves. Cleavage of tRNAs by Angiogenin is a common cellular stress response to silence translational programmes, and we show that Angiogenin binds tRNAs lacking site-specific NSun2-methylation with higher affinity. Furthermore, cells lacking functional NSun2 up-regulate stress markers, and deletion of NSun2 compromises cellular survival in response stress stimuli including UV-light and oxidative stress. The decreased tolerance of NSun2 null cells towards oxidative stress can be rescued through inhibition of Angiogenin. In conclusion, cytosine-5 RNA methylation is an essential post-transcriptional mechanism during cellular stress responses and NSun2-mediated tRNA methylation protects from Angiogenin-dependent stress-induced RNA cleavage. RNA Methylation profiling by high throughput sequencing small non-coding RNA profiling by high throughput sequencing Pol III Chromatin-IP profiling by high throughput sequencing
2014-11-06 | E-GEOD-44746 | biostudies-arrayexpress
Project description:The human genome encodes hundreds of tRNA genes but their individual contribution to the tRNA pool is not fully understood. Deep sequencing of tRNA transcripts (tRNA-Seq) can estimate tRNA abundance at single gene resolution, but tRNA structures and post-transcriptional modifications impair these analyses. Here we present a bioinformatics strategy to investigate differential tRNA gene expression and use it to compare tRNA-Seq datasets from cultured human cells and human brain. We find that sequencing caveats affect quantitation of only a subset of human tRNA genes. Unexpectedly, we detect several cases where the differences in tRNA expression among samples do not involve variations at the level of isoacceptor tRNA sets (tRNAs charged with the same amino acid but using different anticodons); but rather among tRNA genes within the same isodecoder set (tRNAs having the same anticodon sequence). Because isodecoder tRNAs are functionally equal in terms of genetic translation, their differential expression may be related to non-canonical tRNA functions. We show that several instances of differential tRNA gene expression result in changes in the abundance of tRNA-derived fragments (tRFs) but not of mature tRNAs. Examples of differentially expressed tRFs include: PIWI-associated RNAs, tRFs present in tissue samples but not in cells cultured in vitro, and somatic tissue-specific tRFs. Our data support that differential expression of tRNA genes regulate non-canonical tRNA functions performed by tRFs.
2019-04-17 | GSE114904 | GEO
Project description:Tyrosyl-tRNA synthetase was digested with MMPs after which cleavage fragments were resolved using SDS-PAGE. Major bands were digested with trypsin and analyzed by LC-MS/MS.
2019-05-30 | PXD013197 | Pride
Project description:Mutations in the cytosine-5 RNA methyltransferase NSun2 can cause Intellectual Disability (ID) and symptoms commonly found in patients with Dubowitz syndrome. By analysing gene expression data with the global cytosine-5 RNA methylome in NSun2-deficient mice, we find that loss of cytosine-5 RNA methylation increases the fragmentation of transfer RNAs (tRNA) leading to an accumulation of 5’ halves. Cleavage of tRNAs by Angiogenin is a common cellular stress response to silence translational programmes, and we show that Angiogenin binds tRNAs lacking site-specific NSun2-methylation with higher affinity. Furthermore, cells lacking functional NSun2 up-regulate stress markers, and deletion of NSun2 compromises cellular survival in response stress stimuli including UV-light and oxidative stress. The decreased tolerance of NSun2 null cells towards oxidative stress can be rescued through inhibition of Angiogenin. In conclusion, cytosine-5 RNA methylation is an essential post-transcriptional mechanism during cellular stress responses and NSun2-mediated tRNA methylation protects from Angiogenin-dependent stress-induced RNA cleavage.
2014-11-06 | GSE44746 | GEO
Project description:Angiogenin (ANG) is a stress-activated ribonuclease that promotes the survival of motor neurons. Ribonuclease inactivating point mutations are found in a subset of patients with ALS, a fatal neurodegenerative disease with no cure. We recently showed that ANG cleaves tRNA within anticodon loops to produce 5'- and 3'-fragments known as tRNA-derived, stress-induced RNAs (tiRNAs). Selected 5'-tiRNAs (e.g., tiRNA(Ala), tiRNA(Cys)) cooperate with the translational repressor Y-box binding protein 1 (YB-1) to displace the cap-binding complex eIF4F from capped mRNA, inhibit translation initiation, and induce the assembly of stress granules (SGs). Here, we show that translationally active tiRNAs assemble unique G-quadruplex (G4) structures that are required for translation inhibition. We show that tiRNA(Ala) binds the cold shock domain of YB-1 to activate these translational reprogramming events. We discovered that 5'-tiDNA(Ala) (the DNA equivalent of 5'-tiRNA(Ala)) is a stable tiRNA analog that displaces eIF4F from capped mRNA, inhibits translation initiation, and induces the assembly of SGs. The 5'-tiDNA(Ala) also assembles a G4 structure that allows it to enter motor neurons spontaneously and trigger a neuroprotective response in a YB-1-dependent manner. Remarkably, the ability of 5'-tiRNA(Ala) to induce SG assembly is inhibited by G4 structures formed by pathological GGGGCC repeats found in C9ORF72, the most common genetic cause of ALS, suggesting that functional interactions between G4 RNAs may contribute to neurodegenerative disease.
| S-EPMC4280610 | biostudies-literature
Project description:We have performed RNA sequencing after tRNA/tRF overexpression
2018-06-11 | GSE99769 | GEO