Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA328029 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3745600.fastq.gz | Fastqsanger.gz | |||
| SRR3745597.fastq.gz | Fastqsanger.gz | |||
| SRR3745598.fastq.gz | Fastqsanger.gz | |||
| SRR3745599.fastq.gz | Fastqsanger.gz |
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Project description:Mutations in the 3’-5’ exonuclease DIS3L2 are associated with Perlman syndrome and hypersusceptibility to Wilms’ tumorigenesis. Previously, we found that Dis3l2 specifically recognizes and degrades uridylated pre-let-7 microRNA. However, the widespread relevance of Dis3l2-mediated decay of uridylated substrates remains unknown. Here we applied an unbiased RNA immunoprecipitation strategy to identify Dis3l2 targets in mouse embryonic stem cells. The disease-associated long noncoding RNA (lncRNA) Rmrp, 7SL, as well as several other Pol III-transcribed noncoding RNAs (ncRNAs) were among the most highly enriched Dis3l2-bound RNAs. 3’-uridylated Rmrp, 7SL, and snRNA species were highly stabilized in the cytoplasm of Dis3l2-depleted cells. Deep sequencing analysis of Rmrp 3’ ends revealed extensive oligouridylation mainly on transcripts with imprecise ends. We implicate the TUTases Zcchc6/11 in the uridylation of these ncRNAs, and biochemical reconstitution assays demonstrate the sufficiency of TUTase-Dis3l2 for Rmrp decay. This establishes Dis3l2-Mediated Decay (DMD) as a quality control pathway that eliminates aberrant ncRNAs.obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations.
2016-07-08 | GSE84107 | GEO
Project description:Uridylation of various cellular RNA species at the 3’ end has been generally linked to RNA degradation. Uridylated pre-miRNAs in mammals and uridylated mRNAs in fission yeast are targeted by the 3′ to 5′ exoribonuclease DIS3L2. In humans, DIS3L2 mutations have been associated with Perlman syndrome development and Wilms tumor susceptibility. In this work, we employ crosslinking in vivo and immunoprecipitation (CLIP) method to assess the RNA binding capacity of human DIS3L2 on a genome-wide scale. Our study uncovers a broad spectrum of uridylated RNAs in human cytoplasm, which include mature as well as aberrant forms of coding and noncoding RNAs, such as rRNAs, snRNAs, snoRNAs, tRNAs and pre-miRNAs. Most importantly, we have identified that a fraction of Pol II transcription start-site associated transcripts are exported to cytoplasm, where they are targeted by the TUT-DIS3L2 pathway. Moreover, this pathway appears to mainly target RNA regions that form stable secondary structures. Our findings imply the role of DIS3L2 and oligouridylation in general RNA quality control of most, if not all RNA classes.
2016-09-27 | GSE81536 | GEO
Project description:Uridylation of various cellular RNA species at the 3’ end has been generally linked to RNA degradation. Uridylated pre-miRNAs in mammals and uridylated mRNAs in fission yeast are targeted by the 3′ to 5′ exoribonuclease DIS3L2. In humans, DIS3L2 mutations have been associated with Perlman syndrome development and Wilms tumor susceptibility. In this work, we employ crosslinking in vivo and immunoprecipitation (CLIP) method to assess the RNA binding capacity of human DIS3L2 on a genome-wide scale. Our study uncovers a broad spectrum of uridylated RNAs in human cytoplasm, which include mature as well as aberrant forms of coding and noncoding RNAs, such as rRNAs, snRNAs, snoRNAs, tRNAs and pre-miRNAs. Most importantly, we have identified that a fraction of Pol II transcription start-site associated transcripts are exported to cytoplasm, where they are targeted by the TUT-DIS3L2 pathway. Moreover, this pathway appears to mainly target RNA regions that form stable secondary structures. Our findings imply the role of DIS3L2 and oligouridylation in general RNA quality control of most, if not all RNA classes.
2016-09-27 | GSE81534 | GEO
Project description:Rapid and widespread mRNA decay is a previously unappreciated feature of apoptosis. Previous work showed that apoptotic mRNA decay depends on mitochondrial outer membrane permeabilization (MOMP) and the RNA-processing enzymes, TUT4, TUT7, and DIS3L2. Which RNAs are decayed, however, was not known. Here we present RNA-seq data of TRAIL-induced apoptosis in HCT116 cells showing global decay of mRNAs as well as polyadenylated noncoding RNAs, beginning at the 3’-end.
2018-05-01 | GSE104602 | GEO
Project description:The exosome-independent exoribonuclease DIS3L2 is mutated in Perlman syndrome. Here we used extensive global transcriptomic and targeted biochemical analyses to identify novel DIS3L2 substrates in human cells. We show that DIS3L2 regulates pol II transcripts, comprising selected canonical and histone-coding mRNAs, and a novel FTL_short RNA from the ferritin mRNA 5' UTR. Importantly, DIS3L2 contributes to surveillance of pre-snRNAs during their cytoplasmic maturation. Among pol III transcripts, DIS3L2 particularly targets vault and Y RNAs and an Alu-like element BC200 RNA, but not Alu repeats, which are removed by exosome-associated DIS3. Using 3' RACE-Seq, we demonstrate that all novel DIS3L2 substrates are uridylated in vivo by TUT4/TUT7 poly(U) polymerases. Uridylation-dependent DIS3L2-mediated decay can be recapitulated in vitro, thus reinforcing the tight cooperation between DIS3L2 and TUTases. Together these results indicate that catalytically inactive DIS3L2, characteristic of Perlman syndrome, can lead to deregulation of its target RNAs to disturb transcriptome homeostasis.
2016-07-19 | GSE82336 | GEO
Project description:Although most efforts to understand the functions of RNAs packaged in extracellular vesicles (EVs) have focused on mRNAs and miRNAs, recent studies using less-biased sequencing techniques have revealed that tRNAs and other noncoding RNAs (ncRNAs) are far more abundant. However, the extent to which EV ncRNAs resemble overall cellular RNAs and the benefits to host cells of packaging them into EVs remain unknown. Here, we purified EVs from the culture media of mouse and human cells and characterized their RNA components using high throughput sequencing and Northern blotting. We report that EVs are enriched for numerous aberrant ncRNAs, many of which contain oligouridine tails, a modification associated with degradation by Dis3l2, a cytosolic exoribonuclease that degrades defective structured ncRNAs. Both the numbers of EVs released and the fractions of tailed RNAs in EVs increase on Dis3l2 depletion, indicating that packaging of aberrant ncRNAs into EVs occurs in competition with Dis3l2 decay. Upregulation of multiple type I interferon stimulated genes (ISGs) occurs on Dis3l2 depletion, and cells treated with a neutral sphingomyelinase inhibitor that reduces exosome biogenesis also show moderate ISG upregulation, an effect that is enhanced in Dis3l2-depleted cells and accompanied by the accumulation of aberrant ncRNAs in cellular RNA. Thus, Dis3l2 degradation and packaging of aberrant RNAs into vesicles may prevent these RNAs from activating innate immune sensors and triggering an interferon response.
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Project description:Although most efforts to understand the functions of RNAs packaged in extracellular vesicles (EVs) have focused on mRNAs and miRNAs, recent studies using less-biased sequencing techniques have revealed that tRNAs and other noncoding RNAs (ncRNAs) are far more abundant. However, the extent to which EV ncRNAs resemble overall cellular RNAs and the benefits to host cells of packaging them into EVs remain unknown. Here, we purified EVs from the culture media of mouse and human cells and characterized their RNA components using high throughput sequencing and Northern blotting. We report that EVs are enriched for numerous aberrant ncRNAs, many of which contain oligouridine tails, a modification associated with degradation by Dis3l2, a cytosolic exoribonuclease that degrades defective structured ncRNAs. Both the numbers of EVs released and the fractions of tailed RNAs in EVs increase on Dis3l2 depletion, indicating that packaging of aberrant ncRNAs into EVs occurs in competition with Dis3l2 decay. Upregulation of multiple type I interferon stimulated genes (ISGs) occurs on Dis3l2 depletion, and cells treated with a neutral sphingomyelinase inhibitor that reduces exosome biogenesis also show moderate ISG upregulation, an effect that is enhanced in Dis3l2-depleted cells and accompanied by the accumulation of aberrant ncRNAs in cellular RNA. Thus, Dis3l2 degradation and packaging of aberrant RNAs into vesicles may prevent these RNAs from activating innate immune sensors and triggering an interferon response.
2025-12-16 | GSE307561 | GEO
Project description:Although most efforts to understand the functions of RNAs packaged in extracellular vesicles (EVs) have focused on mRNAs and miRNAs, recent studies using less-biased sequencing techniques have revealed that tRNAs and other noncoding RNAs (ncRNAs) are far more abundant. However, the extent to which EV ncRNAs resemble overall cellular RNAs and the benefits to host cells of packaging them into EVs remain unknown. Here, we purified EVs from the culture media of mouse and human cells and characterized their RNA components using high throughput sequencing and Northern blotting. We report that EVs are enriched for numerous aberrant ncRNAs, many of which contain oligouridine tails, a modification associated with degradation by Dis3l2, a cytosolic exoribonuclease that degrades defective structured ncRNAs. Both the numbers of EVs released and the fractions of tailed RNAs in EVs increase on Dis3l2 depletion, indicating that packaging of aberrant ncRNAs into EVs occurs in competition with Dis3l2 decay. Upregulation of multiple type I interferon stimulated genes (ISGs) occurs on Dis3l2 depletion, and cells treated with a neutral sphingomyelinase inhibitor that reduces exosome biogenesis also show moderate ISG upregulation, an effect that is enhanced in Dis3l2-depleted cells and accompanied by the accumulation of aberrant ncRNAs in cellular RNA. Thus, Dis3l2 degradation and packaging of aberrant RNAs into vesicles may prevent these RNAs from activating innate immune sensors and triggering an interferon response.
2025-12-16 | GSE307560 | GEO
Project description:Although most efforts to understand the functions of RNAs packaged in extracellular vesicles (EVs) have focused on mRNAs and miRNAs, recent studies using less-biased sequencing techniques have revealed that tRNAs and other noncoding RNAs (ncRNAs) are far more abundant. However, the extent to which EV ncRNAs resemble overall cellular RNAs and the benefits to host cells of packaging them into EVs remain unknown. Here, we purified EVs from the culture media of mouse and human cells and characterized their RNA components using high throughput sequencing and Northern blotting. We report that EVs are enriched for numerous aberrant ncRNAs, many of which contain oligouridine tails, a modification associated with degradation by Dis3l2, a cytosolic exoribonuclease that degrades defective structured ncRNAs. Both the numbers of EVs released and the fractions of tailed RNAs in EVs increase on Dis3l2 depletion, indicating that packaging of aberrant ncRNAs into EVs occurs in competition with Dis3l2 decay. Upregulation of multiple type I interferon stimulated genes (ISGs) occurs on Dis3l2 depletion, and cells treated with a neutral sphingomyelinase inhibitor that reduces exosome biogenesis also show moderate ISG upregulation, an effect that is enhanced in Dis3l2-depleted cells and accompanied by the accumulation of aberrant ncRNAs in cellular RNA. Thus, Dis3l2 degradation and packaging of aberrant RNAs into vesicles may prevent these RNAs from activating innate immune sensors and triggering an interferon response.
2025-12-16 | GSE307559 | GEO
Project description:The exosome-independent exoribonuclease DIS3L2 is mutated in Perlman syndrome. Here we used extensive global transcriptomic and targeted biochemical analyses to identify novel DIS3L2 substrates in human cells. We show that DIS3L2 regulates pol II transcripts, comprising selected canonical and histone-coding mRNAs, and a novel FTL_short RNA from the ferritin mRNA 5' UTR. Importantly, DIS3L2 contributes to surveillance of pre-snRNAs during their cytoplasmic maturation. Among pol III transcripts, DIS3L2 particularly targets vault and Y RNAs and an Alu-like element BC200 RNA, but not Alu repeats, which are removed by exosome-associated DIS3. Using 3' RACE-Seq, we demonstrate that all novel DIS3L2 substrates are uridylated in vivo by TUT4/TUT7 poly(U) polymerases. Uridylation-dependent DIS3L2-mediated decay can be recapitulated in vitro, thus reinforcing the tight cooperation between DIS3L2 and TUTases. Together these results indicate that catalytically inactive DIS3L2, characteristic of Perlman syndrome, can lead to deregulation of its target RNAs to disturb transcriptome homeostasis. To investigate DIS3L2 functions genome-wide, total RNA samples were collected from model cell lines producing either WT or mut DIS3L2 three days after induction with doxycycline. The RNA samples were rRNA-depleted before preparation of strand-specific total RNA libraries according to the standard TruSeq (Illumina) protocol. TruSeq library preparation favours RNA molecules longer than 200 nt, and shorter transcripts are suboptimal for sequencing via this protocol. Thus, to obtain information about potential DIS3L2 RNA substrates with lengths between 20 and 220 nt, another RNA-Seq was carried out in parallel (with size selection through gel purification). The stable inducible HEK293 cell lines producing DIS3L2 variants were obtained using âpAL_01â and âpAL_02â plasmid constructs and the Flp-In⢠T-REx⢠system according to the manufacturerâs guidelines. âpAL_01â and âpAL_02â plasmids are vectors for co-expression of recoded C-terminal FLAG-tagged DIS3L2 [wild type (WT) variant or its catalytic mutant counterpart (mut), respectively] and sh-miRNAs directed against endogenous DIS3L2 mRNA.
2016-07-19 | E-GEOD-82336 | biostudies-arrayexpress