GEO DataSets

(Submitter supplied) Mutations in the poly(A) ribonuclease (PARN) gene cause telomere diseases including familial idiopathic pulmonary fibrosis (IPF) and dyskeratosis congenita (DC)1,2, but how PARN deficiency impacts telomere maintenance is unclear. Here, using somatic cells and induced pluripotent stem (iPS) cells from DC patients with PARN mutations, we show that PARN is required for the 3′ end maturation of the telomerase RNA component (TERC). more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

9 Samples

Download data: XLS

(Submitter supplied) The telomerase RNA component (TERC) is a critical determinant of cellular self renewal. Poly(A)-specific ribonuclease (PARN) is required for post-transcriptional maturation of TERC. PARN mutations lead to incomplete 3′ end processing and increased destruction of nascent TERC RNA transcripts, resulting in telomerase deficiency and telomere diseases. Here, we determined that overexpression of TERC increased telomere length in PARN-deficient cells and hypothesized that decreasing post-transcriptional 3′ oligo-adenylation of TERC would counteract the deleterious effects of PARN mutations. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

8 Samples

Download data: CSV

(Submitter supplied) We aimed to investigate whether treatment with a small molecule drug RG7834 significantly affected the transcriptome of human embryonic stem cells carrying a pathogenic mutation in the gene DKC1.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

6 Samples

Download data: CSV

(Submitter supplied) Here, we develop nascent RNAend-Seq, in which we isolate nascent RNA and sequence the 3' ends of RNA precursors. Using a pulse-chase experimental design, we follow extended precursors of the telomerase RNA component (hTR) and show that the mature telomerase RNA derives from these species with slow kinetics compared to other small non-coding RNAs. The human disease causing gene PARN further delays maturation of the hTR precursor in PARN- mutant cancer cell lines. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL15520

56 Samples

Download data: XLSX

(Submitter supplied) Genetic lesions that reduce telomerase cause a range of incurable diseases including dyskeratosis congenita (DC) and pulmonary fibrosis (PF), and restoring telomere length in these patients would be curative. Ectopic expression of telomerase reverse transcriptase (TERT) risks cellular immortalization, and how to target telomerase in stem cells throughout the body remains unclear. Here we describe a successful screen for small molecules that augment TERC, the non-coding telomerase RNA component, and thereby specifically elongate telomeres in stem cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: CSV

(Submitter supplied) Poly(A)-specific ribonuclease (PARN) and target of EGR1 protein 1 (TOE1) are nuclear granule-associated deadenylases, whose mutations are linked to multiple human diseases. Here, we applied mTAIL-seq and RNA sequencing (RNA-seq) to systematically identify the substrates of PARN and TOE1 and elucidate their molecular functions. We found that PARN and TOE1 do not modulate the length of mRNA poly(A) tails. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

4 Samples

Download data: CSV

(Submitter supplied) Mutations in genes encoding components of the telomerase holoenzyme complex result in a spectrum of rare genetic disorders known as telomere diseases, including dyskeratosis congenita (DC). A consistent finding in DC due to pathogenic mutations in DKC1, which encodes dyskerin, is decreased steady-state levels of the non-coding RNA component of telomerase (TERC) and thus impaired telomere maintenance. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

16 Samples

Download data: FPKM_TRACKING

(Submitter supplied) Dyskeratosis congenita is a bone marrow failure syndrome characterized by the presence of short telomeres at presentation. The X-linked form is caused by mutations in the gene DKC1, encoding the protein dyskerin. Dyskerin is required for in the assembly and stability of telomerase and is also involved in ribosomal RNA (rRNA) processing where it converts specific uridines to pseudouridine. DC is thought to result from failure to maintain tissues, like blood, that are renewed by stem cell activity, suggesting induced pluripotent stem (iPS) cells from X-linked DC patients may provide information about the mechanisms involved. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL5188

6 Samples

Download data: CEL, CHP

(Submitter supplied) Somatic cell nuclear transfer (SCNT) and induced pluripotent stem cells (iPSCs) represent two major approaches for somatic cell reprogramming. However, little attention has been paid to the ability of these two strategies in rejuvenating cells from donors with aging associated syndrome. Here, we utilized telomerase deficient (Terc-/-) mice to probe this question. SCNT-derived embryonic stem cells (ntESCs) and iPSCs were successfully derived from second generation (G2) and third generation (G3) of Terc-/- mice, and ntESCs showed better differentiation potential and self-renewal ability. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6246

6 Samples

Download data: CEL

(Submitter supplied) Haplo-insufficiency of telomerase genes in humans leads to telomere syndromes such as dyskeratosis congenital and idiopathic pulmonary fibrosis. Generation of pluripotent stem cells from telomerase haplo-insufficient donor cells would provide unique opportunities towards the realization of patient-specific stem cell therapies. Recently, pluripotent human embryonic stem cells (ntESCs) have been efficiently achieved by somatic cell nuclear transfer (SCNT). more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL8389

9 Samples

Download data: TXT

(Submitter supplied) The paired-end next-generation sequencing of all hTR versions of less than 200 nucleotides in length was used to analyze the 3’ end distribution of hTR associated to Flag-tagged versions of PABPN1, hTERT and Dyskerin. In total, we obtained 2,716,342, 3,152,013, and 3,077,395 hTR-specific reads for the PABPN1, hTERT, and Dyskerin purifications, respectively. We found that the majority of polyadenylated telomerase RNA recovered in the PABPN1, hTERT, and Dyskerin purifications had poly(A) tails starting immediately after the annotated hTR 3’ end. more...

Organism:

Homo sapiens

Type:

Other

Platform:

GPL15520

3 Samples

Download data: XLS

(Submitter supplied) Critically short telomeres activate p53-mediated apoptosis, resulting in organ failure and causing malignant transformation. Mutations in genes responsible for telomere maintenance are linked to a number of specific human diseases. We derived induced pluripotent stem cells (iPSCs) from patients with mutations in the TERT and TERC telomerase genes. Telomerase-mutant iPSCs elongated telomeres, but at a lower rate than healthy iPSCs, and the magnitude of the elongation deficit correlated with the specific mutation’s impact on telomerase activity. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL5175

20 Samples

Download data: CEL

(Submitter supplied) Dyskeratosis congenita (DC) is a rare genetic disorder characterized by deficiencies in telomere maintenance leading to very short telomeres and the premature onset of certain age_Related diseases, including pulmonary fibrosis (PF). PF is thought to derive from epithelial failure, particularly that of type II alveolar epithelial (AT2) cells, which are highly dependent on Wnt signaling during development and adult regeneration. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

22 Samples

Download data: TXT

(Submitter supplied) Almost all cellular mRNAs terminate in a 3’ poly(A) tail, the removal of which can induce both translational silencing and mRNA decay. Mammalian cells encode many poly(A)-specific exoribonucleases but their individual roles are poorly understood. Here, we undertook an analysis of the role of PARN deadenylase in mouse myoblasts using global measurements of mRNA decay rates. Our results reveal that a discrete set of mRNAs exhibit altered mRNA decay as a result of PARN depletion and that stabilization is associated with increased poly(A) tail length and translation. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6246

30 Samples

Download data: CEL

(Submitter supplied) We identified a germline heterozygous loss-of-function mutation in ZCCHC8, an RNA exosome targeting component, in a family with autosomal dominant pulmonary fibrosis and telomerase RNA insufficiency. To understand the in vivo consequences of Zcchc8 loss, we targeted the gene locus. Zccchc8+/- showed no significant phenotypes but Zcchc8-/- mice showed severe neurodevelopmental defects and died early in adulthood by 60 days. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

14 Samples

Download data: TXT

(Submitter supplied) Primary telomerase RNA transcripts are processed into shorter mature forms that assemble into a complex with the catalytic subunit and provide the template for telomerase activity. In diverse fungi telomerase RNA 3’ end processing involves a single cleavage reaction by the spliceosome akin to the first step of splicing. Longer forms of human telomerase RNA (hTR) have been reported, but how the mature form of precisely 451 nucleotides is generated is still unknown. more...

Organism:

Homo sapiens

Type:

Other

Platform:

GPL16791

16 Samples

Download data: XLSX

(Submitter supplied) RNA sequencing of HeLa cells treated with siRNA against the RNA exosome components hRRP40, hRRP6, hDIS3, and hRRP6/hDIS3 or the splicing inhibitors Isoginkgetin and spliceostatin A, respectively.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

33 Samples

Download data: TXT