PABPN1 shuts down alternative poly(A) sites.
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ABSTRACT:
SUBMITTER: Simonelig M
PROVIDER: S-EPMC3463261 | biostudies-other | 2012 Oct
REPOSITORIES: biostudies-other
Similar Datasets
Project description:BACKGROUND: Alternative polyadenylation (APA) plays an important role in the post-transcriptional regulation of gene expression. Little is known about how APA sites may evolve in homologous genes in different plant species. To this end, comparative studies of APA sites in different organisms are needed. In this study, a collection of poly(A) sites in Medicago truncatula, a model system for legume plants, has been generated and compared with APA sites in Arabidopsis thaliana. RESULTS: The poly(A) tags from a deep-sequencing protocol were mapped to the annotated M. truncatula genome, and the identified poly(A) sites used to update the annotations of 14,203 genes. The results show that 64% of M. truncatula genes possess more than one poly(A) site, comparable to the percentages reported for Arabidopsis and rice. In addition, the poly(A) signals associated with M. truncatula genes were similar to those seen in Arabidopsis and other plants. The 3'-UTR lengths are correlated in pairs of orthologous genes between M. truncatula and Arabidopsis. Very little conservation of intronic poly(A) sites was found between Arabidopsis and M. truncatula, which suggests that such sites are likely to be species-specific in plants. In contrast, there is a greater conservation of CDS-localized poly(A) sites in these two species. A sizeable number of M. truncatula antisense poly(A) sites were found. A high percentage of the associated target genes possess Arabidopsis orthologs that are also associated with antisense sites. This is suggestive of important roles for antisense regulation of these target genes. CONCLUSIONS: Our results reveal some distinct patterns of sense and antisense poly(A) sites in Arabidopsis and M. truncatula. In so doing, this study lends insight into general evolutionary trends of alternative polyadenylation in plants.
| S-EPMC4117952 | biostudies-literature
Project description:Most eukaryotic mRNAs accommodate alternative sites of poly(A) addition in the 3' untranslated region in order to regulate mRNA function. Here, we present a systematic analysis of 3' end formation factors, which revealed 3'UTR lengthening in response to a loss of the core machinery, whereas a loss of the Sen1 helicase resulted in shorter 3'UTRs. We show that the anti-cancer drug cordycepin, 3' deoxyadenosine, caused nucleotide accumulation and the usage of distal poly(A) sites. Mycophenolic acid, a drug which reduces GTP levels and impairs RNA polymerase II (RNAP II) transcription elongation, promoted the usage of proximal sites and reversed the effects of cordycepin on alternative polyadenylation. Moreover, cordycepin-mediated usage of distal sites was associated with a permissive chromatin template and was suppressed in the presence of an rpb1 mutation, which slows RNAP II elongation rate. We propose that alternative polyadenylation is governed by temporal coordination of RNAP II transcription and 3' end processing and controlled by the availability of 3' end factors, nucleotide levels and chromatin landscape.
| S-EPMC8263057 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-06-25 | GSE160539 | GEO
Project description:RNA-seq reads containing part of the poly(A) tail of transcripts (denoted as poly(A) reads) provide the most direct evidence for the position of poly(A) sites in the genome. However, due to reduced coverage of poly(A) tails by reads, poly(A) reads are not routinely identified during RNA-seq mapping. Nevertheless, recent studies for several herpesviruses successfully employed mapping of poly(A) reads to identify herpesvirus poly(A) sites using different strategies and customized programs. To more easily allow such analyses without requiring additional programs, we integrated poly(A) read mapping and prediction of poly(A) sites into our RNA-seq mapping program ContextMap 2. The implemented approach essentially generalizes previously used poly(A) read mapping approaches and combines them with the context-based approach of ContextMap 2 to take into account information provided by other reads aligned to the same location. Poly(A) read mapping using ContextMap 2 was evaluated on real-life data from the ENCODE project and compared against a competing approach based on transcriptome assembly (KLEAT). This showed high positive predictive value for our approach, evidenced also by the presence of poly(A) signals, and considerably lower runtime than KLEAT. Although sensitivity is low for both methods, we show that this is in part due to a high extent of spurious results in the gold standard set derived from RNA-PET data. Sensitivity improves for poly(A) sites of known transcripts or determined with a more specific poly(A) sequencing protocol and increases with read coverage on transcript ends. Finally, we illustrate the usefulness of the approach in a high read coverage scenario by a re-analysis of published data for herpes simplex virus 1. Thus, with current trends towards increasing sequencing depth and read length, poly(A) read mapping will prove to be increasingly useful and can now be performed automatically during RNA-seq mapping with ContextMap 2.
| S-EPMC5279776 | biostudies-literature
Project description:PAT-seq approach was used to determine changes to 3'UTR length in yeast upon addition of 20µg/ml cordycepin (3'deoxyadenosine) for 0, 5, 10, 20 or 40 minutes
2021-06-25 | GSE160537 | GEO
Project description:PAT-seq approach was used to determine changes to 3'UTR length in yeast upon mutation of NNS subunits Nrd1 (nrd1-5), Nab3 (nab3-11) and Sen1 (sen1-1) compared to wild type cells
2021-06-25 | GSE160567 | GEO
Project description:Poly(A)-ClickSeq is a new methodology for the sequencing of the 3'UTR/poly(A) tail junction of RNA. We analysed both wild-type and CF25Im knock-down HeLa cells in culture using Poly(A)-ClickSeq to find the distribution of poly(A) sites in these samples and determine the role of CF25Im in poly(A) site selection (alternative poly-adenylation, APA).
2017-05-02 | GSE94950 | GEO
Project description:Alternative polyadenylation (APA) contributes to post-transcriptional regulation, but its role in Alzheimer’s disease (AD) is largely unknown. Using high-resolution SQUARE multiple 3’ primer-based sequencing, we discovered massive APA differences in temporal gyrus tissues from demented AD patients compared to either healthy controls or non-demented donors with AD neuropathology (NDWP). Advanced statistics, microfluidics RT-PCR and protein measurements validated known and novel APA-modified 3’-intact transcripts. Moreover, APA modifications, more than total transcript counts, distinguished AD patients from both controls and NDWP donors and identified cell type-characteristic, cognition-associated and neuropathology-related changes. AD-enhanced APA variants included known therapeutic targets of brain, vascular and autoimmune disorders, predicting co-involvement of these target genes in AD progression; AD/NDWP increases in 3’-intact proteinopathy-related hnRNP mRNAs were inversely associated with protein decreases, whereas NDWP-potentiated cognition was accompanied by distinct ATP and mitochondrial variants. APA variations thus provide a novel resource of unique value for both basic and translational neuroscience researchers.
2017-04-27 | GSE57152 | GEO
Project description:mPAT approach using an anchored oligo-dT (TV12VN) primer to determine changes to 3'UTR length in yeast upon cordycepin treatment and new transcription using 4-thiouracil (4tU) labelling of RNA. This appears as a T to C conversion in sequencing reads.
2021-06-25 | GSE160993 | GEO
Project description:BackgroundThe formation of ADP-ribose polymers on target proteins by poly(ADP-ribose) polymerases serves a variety of cell signaling functions. In addition, extensive activation of poly(ADP-ribose) polymerase-1 (PARP-1) is a dominant cause of cell death in ischemia-reperfusion, trauma, and other conditions. Poly(ADP-ribose) glycohydrolase (PARG) degrades the ADP-ribose polymers formed on acceptor proteins by PARP-1 and other PARP family members. PARG exists as multiple isoforms with differing subcellular localizations, but the functional significance of these isoforms is uncertain.Methods / principal findingsPrimary mouse astrocytes were treated with an antisense phosphorodiamidate morpholino oligonucleotide (PMO) targeted to exon 1 of full-length PARG to suppress expression of this nuclear-specific PARG isoform. The antisense-treated cells showed down-regulation of both nuclear PARG immunoreactivity and nuclear PARG enzymatic activity, without significant alteration in cytoplasmic PARG activity. When treated with the genotoxic agent MNNG to induced PARP-1 activation, the antisense-treated cells showed a delayed rate of nuclear PAR degradation, reduced nuclear condensation, and reduced cell death.Conclusions/significanceThese results support a preferentially nuclear localization for full-length PARG, and suggest a key role for this isoform in the PARP-1 cell death pathway.
| S-EPMC2655720 | biostudies-literature