Developmentally regulated long non-coding RNAs in Xenopus tropicalis.
Ontology highlight
ABSTRACT:
SUBMITTER: Forouzmand E
PROVIDER: S-EPMC5233649 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Long intergenic non-coding RNAs (lincRNAs) have been implicated in gene regulation, but their requirement for development needs empirical interrogation. We computationally identified nine murine lincRNAs that have developmentally regulated transcriptional and epigenomic profiles specific to early heart differentiation. Six of the nine lincRNAs had in vivo expression patterns supporting a potential function in heart development, including a transcript downstream of the cardiac transcription factor Hand2, which we named Handlr (Hand2-associated lincRNA), Rubie and Atcayos We genetically ablated these six lincRNAs in mouse, which suggested genomic regulatory roles for four of the cohort. However, none of the lincRNA deletions led to severe cardiac phenotypes. Thus, we stressed the hearts of adult Handlr and Atcayos mutant mice by transverse aortic banding and found that absence of these lincRNAs did not affect cardiac hypertrophy or left ventricular function post-stress. Our results support roles for lincRNA transcripts and/or transcription in the regulation of topologically associated genes. However, the individual importance of developmentally specific lincRNAs is yet to be established. Their status as either gene-like entities or epigenetic components of the nucleus should be further considered.
| S-EPMC6918742 | biostudies-literature
Project description:Genome-wide RNA sequencing has shown that only a small fraction of the human genome is transcribed into protein-coding mRNAs. While once thought to be "junk" DNA, recent findings indicate that the rest of the genome encodes many types of non-coding RNA molecules with a myriad of functions still being determined. Among the non-coding RNAs, long non-coding RNAs (lncRNA) and enhancer RNAs (eRNA) are found to be most copious. While their exact biological functions and mechanisms of action are currently unknown, technologies such as next-generation RNA sequencing (RNA-seq) and global nuclear run-on sequencing (GRO-seq) have begun deciphering their expression patterns and biological significance. In addition to their identification, it has been shown that the expression of long non-coding RNAs and enhancer RNAs can vary due to spatial, temporal, developmental, or hormonal variations. In this review, we explore newly reported information on estrogen-regulated eRNAs and lncRNAs and their associated biological functions to help outline their markedly prominent roles in estrogen-dependent signaling.
| S-EPMC7279485 | biostudies-literature
Project description:MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are components of many signaling pathways associated with tumor aggressiveness and cancer metastasis. Some lncRNAs are classified as competitive endogenous RNAs (ceRNAs) that bind to specific miRNAs to prevent interaction with target mRNAs. Studies have shown that the hepatocyte growth factor/mesenchymal-epithelial transition factor (HGF/c-Met) pathway is involved in physiological and pathological processes such as cell growth, angiogenesis, and embryogenesis. Overexpression of c-Met can lead to sustained activation of downstream signals, resulting in carcinogenesis, metastasis, and resistance to targeted therapies. In this review, we evaluated the effects of anti-oncogenic and oncogenic non-coding RNAs (ncRNAs) on c-Met, and the interactions among lncRNAs, miRNAs, and c-Met in cancer using clinical and tissue chromatin immunoprecipition (ChIP) analysis data. We summarized current knowledge of the mechanisms and effects of the lncRNAs/miR-34a/c-Met axis in various tumor types, and evaluated the potential therapeutic value of lncRNAs and/or miRNAs targeted to c-Met on drug-resistance. Furthermore, we discussed the functions of lncRNAs and miRNAs in c-Met-related carcinogenesis and potential therapeutic strategies.
| S-EPMC7078111 | biostudies-literature
Project description:Colorectal cancer is one of the most common causes of cancer-related deaths worldwide. Despite the advances in the knowledge of pathogenetic molecular mechanisms and the implementation of more effective drug treatments in recent years, the overall survival rate of patients remains unsatisfactory. The high death rate is mainly due to metastasis of cancer in about half of the cancer patients and the emergence of drug-resistant populations of cancer cells. Improved understanding of cancer molecular biology has highlighted the role of non-coding RNAs (ncRNAs) in colorectal cancer development and evolution. ncRNAs regulate gene expression through various mechanisms, including epigenetic modifications and interactions of long non-coding RNAs (lncRNAs) with both microRNAs (miRNAs) and proteins, and through the action of lncRNAs as miRNA precursors or pseudogenes. LncRNAs can also be detected in the blood and circulating ncRNAs have become a new source of non-invasive cancer biomarkers for the diagnosis and prognosis of colorectal cancer, as well as for predicting the response to drug therapy. In this review, we focus on the role of lncRNAs in colorectal cancer development, progression, and chemoresistance, and as possible therapeutic targets.
| S-EPMC9654895 | biostudies-literature
Project description:BACKGROUND: Recent analysis of the mouse transcriptional data has revealed the existence of approximately 34,000 messenger-like non-coding RNAs (ml-ncRNAs). Whereas the functional properties of these ml-ncRNAs are beginning to be unravelled, no functional information is available for the large majority of these transcripts. RESULTS: A few ml-ncRNA have been shown to have genomic loci that overlap with microRNA loci, leading us to suspect that a fraction of ml-ncRNA may encode microRNAs. We therefore developed an algorithm (PriMir) for specifically detecting potential microRNA-encoding transcripts in the entire set of 34,030 mouse full-length ml-ncRNAs. In combination with mouse-rat sequence conservation, this algorithm detected 97 (80 of them were novel) strong miRNA-encoding candidates, and for 52 of these we obtained experimental evidence for the existence of their corresponding mature microRNA by microarray and stem-loop RT-PCR. Sequence analysis of the microRNA-encoding RNAs revealed an internal motif, whose presence correlates strongly (R2 = 0.9, P-value = 2.2 x 10(-16)) with the occurrence of stem-loops with characteristics of known pre-miRNAs, indicating the presence of a larger number microRNA-encoding RNAs (from 300 up to 800) in the ml-ncRNAs population. CONCLUSION: Our work highlights a unique group of ml-ncRNAs and offers clues to their functions.
| S-EPMC2410135 | biostudies-literature
Project description:The human malaria parasite Plasmodium falciparum has a complex and multi-stage life cycle that requires extensive and precise gene regulation to allow invasion and hijacking of host cells, transmission, and immune escape. To date, the regulatory elements orchestrating these critical parasite processes remain largely unknown. Yet it is becoming increasingly clear that long non-coding RNAs (lncRNAs) could represent a missing regulatory layer across a broad range of organisms.To investigate the regulatory capacity of lncRNA in P. falciparum, we harvested fifteen samples from two time-courses. Our sample set profiled 56 h of P. falciparum blood stage development. We then developed and validated strand-specific, non-polyA-selected RNA sequencing methods, and pursued the first assembly of P. falciparum strand-specific transcript structures from RNA sequencing data. This approach enabled the annotation of over one thousand lncRNA transcript models and their comprehensive global analysis: coding prediction, periodicity, stage-specificity, correlation, GC content, length, location relative to annotated transcripts, and splicing. We validated the complete splicing structure of three lncRNAs with compelling properties. Non-polyA-selected deep sequencing also enabled the prediction of hundreds of intriguing P. falciparum circular RNAs, six of which we validated experimentally.We found that a subset of lncRNAs, including all subtelomeric lncRNAs, strongly peaked in expression during invasion. By contrast, antisense transcript levels significantly dropped during invasion. As compared to neighboring mRNAs, the expression of antisense-sense pairs was significantly anti-correlated during blood stage development, indicating transcriptional interference. We also validated that P. falciparum produces circRNAs, which is notable given the lack of RNA interference in the organism, and discovered that a highly expressed, five-exon antisense RNA is poised to regulate P. falciparum gametocyte development 1 (PfGDV1), a gene required for early sexual commitment events.
| S-EPMC4465157 | biostudies-literature
Project description:We previously demonstrated that the oocyte nucleus (germinal vesicle or GV) of Xenopus tropicalis contains a population of stable RNA molecules derived from the introns of most expressed genes. Here we show that similar stable intronic sequence (sis) RNAs occur in the oocyte cytoplasm. About 9000 cytoplasmic sisRNAs have been identified, all of which are resistant to the exonuclease RNase R. About half have been confirmed as lariat molecules and the rest are presumed to be lariats, whereas nuclear sisRNAs are a mixture of lariat and linear molecules. Cytoplasmic sisRNAs are more abundant on a molar basis than nuclear sisRNAs and are derived from short introns, mostly under 1 kb in length. Both nuclear and cytoplasmic sisRNAs are transmitted intact to the egg at GV breakdown and persist until at least the blastula stage of embryogenesis, when zygotic transcription begins. We compared cytoplasmic sisRNAs derived from orthologous genes of X. tropicalis and X. laevis, and found that the specific introns from which sisRNAs are derived are not conserved. The existence of sisRNAs in the cytoplasm of the oocyte, their transmission to the fertilized egg, and their persistence during early embryogenesis suggest that they might play a regulatory role in mRNA translation.
| S-EPMC4138330 | biostudies-literature
Project description:Acute myeloid leukemia (AML) represents 80% of adult leukemias and 15-20% of childhood leukemias. AML are characterized by the presence of 20% blasts or more in the bone marrow, or defining cytogenetic abnormalities. Laboratory diagnoses of myelodysplastic syndromes (MDS) depend on morphological changes based on dysplasia in peripheral blood and bone marrow, including peripheral blood smears, bone marrow aspirate smears, and bone marrow biopsies. As leukemic cells are not functional, the patient develops anemia, neutropenia, and thrombocytopenia, leading to fatigue, recurrent infections, and hemorrhage. The genetic background and associated mutations in AML blasts determine the clinical course of the disease. Over the last decade, non-coding RNAs transcripts that do not codify for proteins but play a role in regulation of functions have been shown to have multiple applications in the diagnosis, prognosis and therapeutic approach of various types of cancers, including myeloid malignancies. After a comprehensive review of current literature, we found reports of multiple long non-coding RNAs (lncRNAs) that can differentiate between AML types and how their exogenous modulation can dramatically change the behavior of AML cells. These lncRNAs include: H19, LINC00877, RP11-84C10, CRINDE, RP11848P1.3, ZNF667-AS1, AC111000.4-202, SFMBT2, LINC02082-201, MEG3, AC009495.2, PVT1, HOTTIP, SNHG5, and CCAT1. In addition, by performing an analysis on available AML data in The Cancer Genome Atlas (TCGA), we found 10 lncRNAs with significantly differential expression between patients in favorable, intermediate/normal, or poor cytogenetic risk categories. These are: DANCR, PRDM16-DT, SNHG6, OIP5-AS1, SNHG16, JPX, FTX, KCNQ1OT1, TP73-AS1, and GAS5. The identification of a molecular signature based on lncRNAs has the potential for have deep clinical significance, as it could potentially help better define the evolution from low-grade MDS to high-grade MDS to AML, changing the course of therapy. This would allow clinicians to provide a more personalized, patient-tailored therapeutic approach, moving from transfusion-based therapy, as is the case for low-grade MDS, to the introduction of azacytidine-based chemotherapy or allogeneic stem cell transplantation, which is the current treatment for high-grade MDS.
| S-EPMC6813191 | biostudies-literature
Project description:Less than 2% of the genome encodes for proteins. Accumulating studies have revealed a diverse set of RNAs derived from the non-coding genome. Among them, long non-coding RNAs (lncRNAs) have garnered widespread attention over recent years as emerging regulators of diverse biological processes including in cardiovascular disease (CVD). However, our knowledge of their mechanisms by which they control CVD-related gene expression and cell signaling pathways is still limited. Furthermore, only a handful of lncRNAs has been functionally evaluated in the context of vascular inflammation, an important process that underlies both acute and chronic disease states. Because some lncRNAs may be expressed in cell- and tissue-specific expression patterns, these non-coding RNAs hold great promise as novel biomarkers and as therapeutic targets in health and disease. Herein, we review those lncRNAs implicated in pro- and anti-inflammatory processes of acute and chronic vascular inflammation. An improved understanding of lncRNAs in vascular inflammation may provide new pathophysiological insights in CVD and opportunities for the generation of a new class of RNA-based biomarkers and therapeutic targets.
| S-EPMC5890095 | biostudies-literature
Project description:Recent advances in next-generation sequencing technology in transcriptome analysis have helped identify numerous non-coding RNAs. The long non-coding RNA (lncRNA) is commonly defined as an RNA molecule with a length of 200 bp-100 kbp that lacks protein-coding potential. LncRNAs play a critical role in the regulation of gene expression, including chromatin modification, transcription and post-transcriptional processing. It has been confirmed that dysregulation of lncRNAs is associated with a number of human diseases, particularly tumors. In this study, we focused on the most extensively investigated lncRNAs in hepatocellular carcinoma (HCC). The biological functions and molecular mechanisms of the majority of lncRNAs have yet to be investigated. The improved knowledge on lncRNAs in HCC may help identify lncRNAs that may be used as novel prognostic markers and therapeutic targets.
| S-EPMC4251171 | biostudies-literature