PIWI-interacting RNAs as novel regulators of pancreatic beta-cell function
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE93792 | GEO | 2017/06/29
SECONDARY ACCESSION(S): PRJNA362355
REPOSITORIES: GEO
Similar Datasets
Project description:There is mounting evidence indicating that piRNAs are also present in somatic cells where they may accomplish additional regulatory tasks. The aim of this study was to identify the piRNAs expressed in pancreatic islets and to determine whether they are involved in the control of beta-cell activities. piRNA profiling of rat pancreatic islets was performed by microarray. We detected about 18’000 piRNAs in rat pancreatic islets, many of which were differentially expressed throughout islet postnatal development.
2017-06-29 | GSE93790 | GEO
Project description:There is mounting evidence indicating that piRNAs are also present in somatic cells where they may accomplish additional regulatory tasks. The aim of this study was to identify the piRNAs expressed in pancreatic islets and to determine whether they are involved in the control of beta-cell activities. piRNA profiling of rat pancreatic islets was performed by microarray. We detected about 18’000 piRNAs in rat pancreatic islets, many of which were differentially expressed throughout islet of Goto-Kakizaki rats, a well-established model of Type 2 diabetes.
2017-06-29 | GSE93791 | GEO
Project description:PIWI-interacting RNAs as novel regulators of pancreatic beta-cell function
| PRJNA362355 | ENA
Project description:PIWI proteins and their bound PIWI-interacting RNAs (piRNAs) are found in animal germlines and are essential for fertility, but their functions outside of the gonad are not well understood. The cnidarian Hydra is a simple metazoan with well-characterized stem/progenitor cells that provides a unique model for analysis of PIWI function. Here we report that Hydra has two PIWI proteins, Hydra PIWI (Hywi) and Hydra PIWI-like (Hyli), both of which are expressed in all Hydra stem/progenitor cells, but not in terminally differentiated cells. We identified ∼15 million piRNAs associated with Hywi and/or Hyli and found that they exhibit the ping-pong signature of piRNA biogenesis. Hydra PIWI proteins are strictly cytoplasmic and thus likely act as posttranscriptional regulators. To explore this function, we generated a Hydra transcriptome for piRNA mapping. piRNAs map to transposons with a 25- to 35-fold enrichment compared with the abundance of transposon transcripts. By sequencing the small RNAs specific to the interstitial, ectodermal, and endodermal lineages, we found that the targeting of transposons appears to be largely restricted to the interstitial lineage. We also identified putative nontransposon targets of the pathway unique to each lineage. Finally we demonstrate that hywi function is essential in the somatic epithelial lineages. This comprehensive analysis of the PIWI-piRNA pathway in the somatic stem/progenitor cells of a nonbilaterian animal suggests that this pathway originated with broader stem cell functionality.
| S-EPMC3890812 | biostudies-literature
Project description:Piwi-interacting RNAs (piRNAs), whose role in germline maintenance has been established, are now also being classified as post-transcriptional regulators of gene expression in somatic cells. PIWI proteins, central to piRNA biogenesis, have been identified as genetic and epigenetic regulators of gene expression. piRNAs/PIWIs have emerged as potential biomarkers for cancer but their relevance to breast cancer has not been comprehensively studied. piRNAs and mRNAs were profiled from normal and breast tumor tissues using next generation sequencing and Agilent platforms, respectively. Gene targets for differentially expressed piRNAs were identified from mRNA expression dataset. piRNAs and PIWI genes were independently assessed for their prognostic significance (outcomes: Overall Survival, OS and Recurrence Free Survival, RFS). We discovered eight piRNAs as novel independent prognostic markers and their association with OS was confirmed in an external dataset (The Cancer Genome Atlas). Further, PIWIL3 and PIWIL4 genes showed prognostic relevance. 306 gene targets exhibited reciprocal relationship with piRNA expression. Cancer cell pathways such as apoptosis and cell signaling were the key Gene Ontology terms associated with the regulated gene targets. Overall, we have captured the entire cascade of events in a dysregulated piRNA pathway and have identified novel markers for breast cancer prognostication.
| S-EPMC5122362 | biostudies-literature
Project description:PIWI-interacting RNAs (piRNAs) are small non-coding RNAs that partner with PIWI proteins to protect germline tissues from destabilizing transposon activity. While the aberrant expression of PIWI proteins has been linked with poor outcomes for many cancers, less is known about the expression or function of piRNAs in cancer. We performed array-based piRNA expression profiling in seven pairs of normal and glioblastoma multiforme (GBM) tissue specimens and identified expression of ~350 piRNAs in both tissues and a subset with dysregulated expression in GBM. Several down-regulated piRNAs inhibited proliferation when transfected into glioma cell lines while those equivalently expressed in tumor and normal tissues did not, consistent with piRNA-specific tumor-suppressive roles. Upregulation of the most underexpressed piRNA, piR-8041, was found to induce cell cycle arrest and apoptosis and to alter transcriptional levels of several genes involved in stress and cell survival pathways. Additionally, the volume of intracranial mouse xenograft tumors was significantly reduced for approximately ten days after pre-implantation transfection with piR-8041. Taken together, our study reveals a previously unidentified functional role for piRNAs as tumor suppressors in gliomagenesis, and suggests that restoration of piRNA levels may be a potential strategy for GBM therapy.
2016-06-04 | GSE79438 | GEO
Project description:PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that bind PIWI family proteins exclusively expressed in the germ cells of mammalian gonads. MIWI2-associated piRNAs are essential for silencing transposons during primordial germ cell development, and MIWI-bound piRNAs are required for normal spermatogenesis during adulthood in mice. Although piRNAs have long been regarded as germ cell-specific, increasing lines of evidence suggest that somatic cells also express piRNA-like RNAs (pilRNAs). Here, we report the detection of abundant pilRNAs in somatic cells, which are similar to MIWI-associated piRNAs mainly expressed in pachytene spermatocytes and round spermatids in the testis. Based on small RNA deep sequencing and quantitative PCR analyses, pilRNA expression is dynamic and displays tissue specificity. Although pilRNAs are similar to pachytene piRNAs in both size and genomic origins, they have a distinct ping-pong signature. Furthermore, pilRNA biogenesis appears to utilize a yet to be identified pathway, which is different from all currently known small RNA biogenetic pathways. In addition, pilRNAs appear to preferentially target the 3'-UTRs of mRNAs in a partially complementary manner. Our data suggest that pilRNAs, as an integral component of the small RNA transcriptome in somatic cell lineages, represent a distinct population of small RNAs that may have functions similar to germ cell piRNAs.
| S-EPMC4239631 | biostudies-literature
Project description:BackgroundPiwi-interacting RNAs (piRNAs) have emerged as potential novel indicators for various diseases; however, their diagnostic value for brucellosis remains unclear. This study aimed to evaluate the diagnostic potential of altered serum piRNAs in patients with brucellosis.MethodsIllumina sequencing via synthesis (SBS) technology was used to screen the serum piRNA profile in brucellosis patients, and markedly dysregulated piRNAs were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) assay in two sets from a cohort of 73 brucellosis patients and 65 controls.ResultsIllumina SBS technology results showed that seven piRNAs were markedly elevated in brucellosis patients compared to normal controls. The seven upregulated piRNAs were further validated individually by qRT-PCR, of which three piRNAs (piR-000753, piR-001312, and piR-016742) were confirmed to be significantly and steadily increased in the patients (> 2-fold, P < 0.01). The area under the receiver operating characteristic (ROC) curve (AUCs) for the three piRNAs ranged from 0.698 to 0.783. The AUC for the three piRNAs combination was 0.772, with a specificity of 86% and a positive predictive value of 90%, respectively.ConclusionsThe three-piRNA panel identified in this study has potential as a novel blood-based auxiliary tool for brucellosis detection.
| S-EPMC9519857 | biostudies-literature
Project description:PIWI-interacting RNAs (piRNAs) are at the center of a small RNA-based immune system that defends genomes against the deleterious action of mobile genetic elements (transposons). PiRNAs are highly variable in sequence with extensive targeting potential. Their diversity is restricted by their preference to start with a Uridine (U) at the 5' most position (1U-bias), a bias that remains poorly understood. Here we uncover that the 1U-bias of Piwi-piRNAs is established by consecutive discrimination against all nucleotides but U, first during piRNA biogenesis and then upon interaction with Piwi's specificity loop. Sequence preferences during piRNA processing also restrict U across the piRNA body with the potential to directly impact target recognition. Overall, the uncovered signatures could modulate specificity and efficacy of piRNA-mediated transposon restriction, and provide a substrate for purifying selection in the ongoing arms race between genomes and their mobile parasites.
| S-EPMC6381166 | biostudies-literature
Project description:Involved with important cellular or gene functions and implicated with many kinds of cancers, piRNAs, or piwi-interacting RNAs, are of small non-coding RNA with around 19-33 nt in length. Given a small non-coding RNA molecule, can we predict whether it is of piRNA according to its sequence information alone? Furthermore, there are two types of piRNA: one has the function of instructing target mRNA deadenylation, and the other does not. Can we discriminate one from the other? With the avalanche of RNA sequences emerging in the postgenomic age, it is urgent to address the two problems for both basic research and drug development. Unfortunately, to the best of our knowledge, so far no computational methods whatsoever could be used to deal with the second problem, let alone deal with the two problems together. Here, by incorporating the physicochemical properties of nucleotides into the pseudo K-tuple nucleotide composition (PseKNC), we proposed a powerful predictor called 2L-piRNA. It is a two-layer ensemble classifier, in which the first layer is for identifying whether a query RNA molecule is piRNA or non-piRNA, and the second layer for identifying whether a piRNA is with or without the function of instructing target mRNA deadenylation. Rigorous cross-validations have indicated that the success rates achieved by the proposed predictor are quite high. For the convenience of most biologists and drug development scientists, the web server for 2L-piRNA has been established at http://bioinformatics.hitsz.edu.cn/2L-piRNA/, by which users can easily get their desired results without the need to go through the mathematical details.
| S-EPMC5415553 | biostudies-literature