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Differentiation of syncytialized trophoblasts elicits widespread 3’UTR shortening that accompanies increased cellular function in protein secretion

ABSTRACT: Differentiation of syncytialized trophoblasts elicits widespread 3’UTR shortening that accompanies increased cellular function in protein secretion

PROVIDER: PRJNA577069 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10267015.fastq.gz	Fastqsanger.gz
	SRR10267016.fastq.gz	Fastqsanger.gz
	SRR10267017.fastq.gz	Fastqsanger.gz
	SRR10267018.fastq.gz	Fastqsanger.gz
	SRR10267019.fastq.gz	Fastqsanger.gz

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Similar Datasets

Differentiation of syncytialized trophoblasts elicits widespread 3’UTR shortening that accompanies increased cellular function in protein secretion

Project description:Most eukaryotic genes express alternative polyadenylation (APA) isoforms with different 3’UTR sizes. The APA profile varies across tissue types and under different growth and differentiation conditions. Here we report that, unlike many other cell differentiation lineages, differentiation of syncytiotrophoblasts (SCTs) elicits widespread 3’UTR shortening, as shown in multiple in vitro trophoblast differentiation models as well as in single placental cells at different stages of pregnancy. We show that the 3’UTR shortening is unrelated to cell proliferation, a feature previously associated with 3’UTR size control, but rather accompanies increased cell function in protein secretion. In addition, 3’UTR shortening correlates with increased transcript abundance and is coupled with enhanced intronic APA site usage, suggesting activation of 3’ end processing in SCT differentiation. Together, our data indicate that SCTs utilize APA to express transcripts with short 3’UTRs, which may enhance hormone production and secretion, contributing to their functions in pregnancy.

2020-05-15 | GSE138759 | GEO

Cellular stress alters 3’UTR landscape through alternative polyadenylation and isoform-specific degradation

Project description:Most eukaryotic genes express alternative polyadenylation (APA) isoforms with different lengths of 3’ untranslated region (3’UTR). Here we show arsenic stress elicits global shortening of 3’UTRs through two mechanisms. First, stress leads to immediate shortening of 3’UTR due to preferential usage of proximal cleavage and polyadenylation sites (PASs), as revealed by 3’ end sequencing of newly made RNAs that are metabolically labeled with 4-thiouridine. Second, long 3’UTR isoforms are more rapidly degraded during recovery from stress as compared to short 3’UTR isoforms, further shortening 3’UTR lengths in the cell. Using ribonucleoprotein immunoprecipitation coupled with 3’ end sequencing (3’READS+RIP), we show that the RNA-binding protein T cell-restricted intracellular antigen-1 (Tia1) preferentially interacts with long 3’UTR isoforms via U-rich elements in alternative 3’UTR sequences, and the interaction correlates with stress granule (SG) association during stress and with mRNA decay during recovery from stress, indicating SG-mediated RNA clearance mechanism post stress. Importantly, genes whose 3’UTRs are shortened by APA during stress can evade stress-induced 3’UTR size-based mRNA degradation, leading to higher transcript abundance post stress. Moreover, proliferating and differentiated cells display different extents of 3’UTR shortening after stress, indicating cell type-specific of impact of stress on the 3’UTR landscape. Together, our data indicate that 3’UTR length plays important roles in gene expression in stressed cells, and APA functions as an adaptive stress response mechanism to preserve mRNAs.

2018-06-13 | GSE101851 | GEO

Constitutive expression of EGR4 elicits cell cycle shortening in primary mesenchymal cells.

Project description:Transcription factors of EGR family mediate cellular responses to MAPK signaling. Albeit working in parallel to proliferation associated AP-1 factors their involvement in cell cycle regulation has not been demonstrated so far. This work reveals pronounced cell cycle shortening following constitutive EGR4 expression in primary mesenchymal cells. Corresponding changes in gene expression provide insight into the molecular mechanism of the effect. Comparison of expression profiles of chicken primary skin fibroblasts infected with retroviral construct SFCVneo-EGR4 versus chicken primary skin fibroblasts infected with empty retroviral vector SFCVneo. Three biological replicates were analyzed for each group.

2010-04-06 | E-GEOD-15143 | biostudies-arrayexpress

Transcript shortening through alternative polyadenylation promotes gene expression during fracture healing

Project description:Maturation of the 3¢ end of almost all eukaryotic messenger RNAs (mRNAs) requires cleavage and polyadenylation. Most mammalian mRNAs are polyadenylated at different sites within the last exon, generating alternative polyadenylation (APA) isoforms that have the same coding region but distinct 3¢ untranslated regions (UTRs). The 3¢UTR contains motifs that regulate mRNA metabolism; thus, changing the 3¢UTR length via APA can significantly impact gene expression. Endochondral ossification is a central process in bone healing, and the impact of APA on gene expression during this process is unknown. Here, we report widespread utilization of APA that impacts multiple pathways with established roles in bone healing. Importantly, progression of endochondral ossification is typified by global 3¢UTR shortening that is coupled with an increased abundance of shortened transcripts as compared to all other transcripts, underscoring the role of APA in promoting gene expression during endochondral bone formation. Our mechanistic studies of genes that undergo APA in the fracture callus uncover an intricate regulatory network in which APA boosts the expression of collagen, type I, alpha 1 (Col1a1) and Col1a2 genes, which encode the 2 subunits of the abundantly expressed protein collagen 1. APA does so via shortening the 3¢UTRs of Col1a1 and Col1a2 mRNAs, which removes the binding sites of miR-29a-3p that otherwise potently triggered the degradation of both transcripts. Taken together, our study takes the lead in characterizing crucial roles of APA in tailoring the 3¢UTR landscape and regulating gene expression during fracture healing.

2023-01-11 | GSE205053 | GEO

Transcriptional characterization of primary human HLA-G+ extravillous trophoblasts (EVT) and Villous trophoblasts (VT)

Project description:Seven patient paired primary human HLA-G+ extravillous trophoblasts (EVT) and Villous trophoblasts (VT) obtained from 1st trimester (7-9 weeks) villous tissue were obtained. RNA was isolated directly after isolation and purification using FACS sort for CD45-HLA-G+ (EVT) and CD45-HLA-G-EGFR1+ (VT) fractions. Expression profiles were compared to two samples of the choriocarcinoma cell line JEG-3 and four samples of decidual stromal cells (DSC) at passage 2 after cell culture.

2015-05-15 | E-MTAB-3217 | biostudies-arrayexpress

Telomere Shortening Impairs PGC Fate Decision

Project description:Telomere Shortening Impairs PGC Fate Decision

| PRJNA660792 | ENA

The systematic shortening of 3’ UTRs has limited influence on the relative change in protein abundance in proliferating cells

Project description:Alternative polyadenylation is an important cellular mechanism that enables generation of mRNA isoforms that differ in their 3' untranslated regions (3' UTRs) and consequently in their susceptibility to miRNA and RNA binding protein mediated regulation. A dramatic change in polyadenylation site usage, leading to the systematic expression of short 3’ UTR isoforms is known to occur upon induction of proliferation in resting cells. To understand the functional consequences of short 3’ UTR isoform expression we used 3' end sequencing and quantitative mass spectroscopy to determine polyadenylation site use, mRNA and protein levels in murine and human naive and activated T cells. We found that while the process and its impact on the susceptibility to miRNA and RNA binding protein mediated regulation are evolutionarily conserved, the conservation is poor at the level of individual orthologous genes. Contrary to the common belief, we did not find that transcriptome-wide 3' UTR shortening leads to a matched increase in mRNA and protein levels of genes with tandem polyadenylation sites. 3' ends of transcripts were profiled by high-throughput sequencing in murine and human naive and activated T cells.

2014-09-25 | E-GEOD-54950 | biostudies-arrayexpress

Dynamic 3'UTR changes during naïve CD4+ T cell activation and proliferation are reverted in the effector/memory state [A-Seq]

Project description:3’ untranslated regions (3’UTRs) are critical elements of most messenger RNA species and can contain binding sites for RNA-binding proteins (RBP) and microRNAs that affect various aspects of RNA life cycles including transcript stability. Cells of the adaptive immune system undergo massive expansion during the effector phase of the immune response and dynamically modify their 3’UTRs in a response to T cell receptor activation. Whether this phenomenon is a secondary effect of proliferation or a mechanism to directly regulate the abundance of specific mRNAs remains unclear. To study 3’UTR dynamics in T helper cells we investigated division-dependent alternative polyadenylation and observed a transient character of global 3’UTR shortening/lengthening in T helper cells that return to a naïve-like polyadenylation state after effector phase expansion. We also showed that 3’UTR lengthening is associated with higher transcript abundance and post-transcriptional regulation than 3’UTR shortening. Sequence analysis of conserved microRNA and RBP binding sites located within varying 3’ UTR regions highlighted the putative involvement of several microRNAs during this process. Our study emphasizes the value of polyadenylation isoforms analysis for understanding cell behaviors, revealing new aspects of the highly complex interplay of transcriptional and post-transcriptional layers in triggering transcript abundance.

2023-11-06 | GSE183424 | GEO

Dynamic Deposition of the Histone H3.3 Variant Accompanies Developmental Remodeling of Arabidopsis Transcriptome

Project description:This SuperSeries is composed of the following subset Series: GSE36626: Dynamic Deposition of the Histone H3.3 Variant Accompanies Developmental Remodeling of Arabidopsis Transcriptome (mRNA-Seq) GSE36629: Dynamic Deposition of the Histone H3.3 Variant Accompanies Developmental Remodeling of Arabidopsis Transcriptome (ChIP-Seq) Refer to individual Series

2012-05-15 | E-GEOD-36631 | biostudies-arrayexpress

Primary term human trophoblasts exposed to ionizing irradiation

Project description:Primary term human trophoblasts were derived from placentas after a healthy pregnancy, and exposed to ionizing irradiation (vs sham) in vitro Primary human trophoblasts were irradiated 24 h after initial plating, defined as time zero. Cells were irradiated at 10 Gy using a Clinac 600C (Varian Medical Systems, Palo Alto, CA) with a 6 MV photon beam and a dose rate of 250 cGy/min. The flasks containing the cells were placed on 1.5 cm of bolus (a tissue equivalent material) since the maximum irradiation depth was 1.5 cm, which corresponded to the plated cell layer. Cells were analyzed 4, 8, and 24 h after irradiation or sham.

2013-08-16 | E-GEOD-49922 | biostudies-arrayexpress

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