scholarly journals miR-183/96/182 cluster is an important morphogenetic factor targeting PAX6 expression in differentiating human retinal organoids

2020 ◽  
Author(s):  
Lucie Peskova ◽  
Denisa Jurcikova ◽  
Tereza Vanova ◽  
Jan Krivanek ◽  
Michaela Capandova ◽  
...  

AbstractMicroRNAs (miRNAs), a class of small, non-coding RNA molecules represent important regulators of gene expression. Recent reports have implicated their role in the cell specification process acting as “fine-tuners” to ensure the precise gene expression at the specific stage of cell differentiation. Here we used retinal organoids differentiated from human pluripotent stem cells (hPSCs) as a model to closely investigate the role of a sensory organ-specific and evolutionary conserved miR-183/96/182 cluster. Using a miRNA tough decoy approach, we inhibited the miR-183/96/182 cluster in hPSCs. Inhibition of the miRNA cluster resulted in an increased expansion of neuroepithelium leading to abnormal “bulged” neural retina in organoids, associated with upregulation of neural-specific and retinal-specific genes. Importantly, we identified PAX6, a well-known essential gene in neuroectoderm specification, as a target of the miR-183/96/182 cluster members. Taken together, the miR-183/96/182 cluster not only represents an important regulator of PAX6 expression, but it also plays a crucial role in retinal tissue morphogenesis.

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4615 ◽  
Author(s):  
Lan Jiang ◽  
Qingqing Wang ◽  
Jue Yu ◽  
Vinita Gowda ◽  
Gabriel Johnson ◽  
...  

The budgerigar (Melopsittacus undulatus) is one of the most widely studied parrot species, serving as an excellent animal model for behavior and neuroscience research. Until recently, it was unknown how sexual differences in the behavior, physiology, and development of organisms are regulated by differential gene expression. MicroRNAs (miRNAs) are endogenous short non-coding RNA molecules that can post-transcriptionally regulate gene expression and play a critical role in gonadal differentiation as well as early development of animals. However, very little is known about the role gonadal miRNAs play in the early development of birds. Research on the sex-biased expression of miRNAs in avian gonads are limited, and little is known aboutM. undulatus. In the current study, we sequenced two small non-coding RNA libraries made from the gonads of adult male and female budgerigars using Illumina paired-end sequencing technology. We obtained 254 known and 141 novel miRNAs, and randomly validated five miRNAs. Of these, three miRNAs were differentially expressed miRNAs and 18 miRNAs involved in sexual differentiation as determined by functional analysis with GO annotation and KEGG pathway analysis. In conclusion, this work is the first report of sex-biased miRNAs expression in the budgerigar, and provides additional sequences to the avian miRNAome database which will foster further functional genomic research.


2020 ◽  
Vol 21 (8) ◽  
pp. 2742 ◽  
Author(s):  
Allan Böhm ◽  
Marianna Vachalcova ◽  
Peter Snopek ◽  
Ljuba Bacharova ◽  
Dominika Komarova ◽  
...  

Micro ribonucleic acids (miRNAs) are short non-coding RNA molecules responsible for regulation of gene expression. They are involved in many pathophysiological processes of a wide spectrum of diseases. Recent studies showed their involvement in atrial fibrillation. They seem to become potential screening biomarkers for atrial fibrillation and even treatment targets for this arrhythmia. The aim of this review article was to summarize the latest knowledge about miRNA and their molecular relation to the pathophysiology, diagnosis and treatment of atrial fibrillation.


2011 ◽  
Vol 121 (4) ◽  
pp. 141-158 ◽  
Author(s):  
Reinhold Munker ◽  
George A. Calin

The diagnosis of cancer has undergone major changes in the last 40 years. Once based purely on morphology, diagnosis has come to incorporate immunological, cytogenetic and molecular methods. Many cancers, especially leukaemias, are now defined by molecular markers. Gene expression profiling based on mRNA has led to further refinement of the classification and diagnosis of cancer. More recently, miRNAs (microRNAs), among other small non-coding RNA molecules, have been discovered and found to be major players in cell biology. miRNAs, having both oncogenic and tumour-suppressive functions, are dysregulated in many types of cancer. miRNAs also interfere with metastasis, apoptosis and invasiveness of cancer cells. In the present review, we discuss recent advances in miRNA profiling in human cancer. We discuss both frequent and rare tumour types and give an outlook on future developments.


MicroRNAs (miRNAs or miRs) are a type of non-coding RNA molecules that regulate the gene expression in a negative way, by downregulating the gene expression mainly at the post-transcriptional level, either by the mRNA degradation process or the inhibition of the translation. The role that many miRNAs play in the pathogenesis of several diseases is well known, such as in the inflammation process, in several steps of the oncogenesis or the metabolism of several virus and bacteria among many others. One of the main limitations in the therapeutic use of miRNAs is the ability to reach the target, as well as doing so without causing any collateral damage. One microRNA can indeed regulate up to 200 target-genes, and one gene can be influenced by a lot of different microRNAs. This is the purpose of the Bio Immune(G)ene Medicine: to achieve the cell without harm, use all the molecular resources available, especially epigenetic with the microRNAs, and to restore the cell homeostasis. The Bio Immune(G)ene Medicine only seeks to play a regulatory biomimetic role, to give the cell the needed information for its own right regulation. Our experience in cell regulation for the past few years has shown the way to fight, for instance, against the deleterious effects of viruses or bacteria in the lymphocytes, also at the background of many autoimmune or allergic diseases, as well as to regulate many other pathological processes. To fulfil this purpose, nanobiotechnology is used to reach the targets; we thus introduce very low doses of miRNAs in nano compounds with the aim to promote the regulation of the main signalling pathways disturbed in a given pathology.


2020 ◽  
Vol 25 (41) ◽  
pp. 4368-4378 ◽  
Author(s):  
Mahesh Mundalil Vasu ◽  
Puthiripadath S. Sumitha ◽  
Parakkal Rahna ◽  
Ismail Thanseem ◽  
Ayyappan Anitha

Background: Efforts to unravel the extensive impact of the non-coding elements of the human genome on cell homeostasis and pathological processes have gained momentum over the last couple of decades. miRNAs refer to short, often 18-25 nucleotides long, non-coding RNA molecules which can regulate gene expression. Each miRNA can regulate several mRNAs. Methods: This article reviews the literature on the roles of miRNAs in autism. Results: Considering the fact that ~ 1% of the human DNA encodes different families of miRNAs, their overall impact as critical regulators of gene expression in the mammalian brain should be immense. Though the autism spectrum disorders (ASDs) are predominantly genetic in nature and several candidate genes are already identified, the highly heterogeneous and multifactorial nature of the disorder makes it difficult to identify common genetic risk factors. Several studies have suggested that the environmental factors may interact with the genetic factors to increase the risk. miRNAs could possibly be one of those factors which explain this link between genetics and the environment. Conclusion: In the present review, we have summarized our current knowledge on miRNAs and their complex roles in ASD, and also on their therapeutic applications.


2015 ◽  
Vol 6 (2) ◽  
pp. 149-155 ◽  
Author(s):  
Pál Perge ◽  
Zoltán Nagy ◽  
Ivan Igaz ◽  
Peter Igaz

AbstractMicroRNAs are short non-coding RNA molecules encoded by distinct genes involved in the posttranscriptional regulation of gene expression. Forming part of the epigenetic machinery, microRNAs are involved in several aspects of tumorigenesis. Deregulation of microRNA expression is a common feature of tumors. Overexpressed oncogenic and underexpressed tumor suppressor microRNAs have been described in many different tumors. MicroRNAs are released from tumors that might affect other cells within and outside the tumor. Circulating microRNAs might also be involved in a tumor surveillance mechanism. In this short overview, some important aspects of microRNA in tumors are discussed.


2021 ◽  
Vol 23 (1) ◽  
pp. 90
Author(s):  
Valeria Domenica Zingale ◽  
Agnese Gugliandolo ◽  
Emanuela Mazzon

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level and that play an important role in many cellular processes, including modulation of inflammation. MiRNAs are present in high concentrations in the central nervous system (CNS) and are spatially and temporally expressed in a specific way. Therefore, an imbalance in the expression pattern of these small molecules can be involved in the development of neurological diseases. Generally, CNS responds to damage or disease through the activation of an inflammatory response, but many neurological disorders are characterized by uncontrolled neuroinflammation. Many studies support the involvement of miRNAs in the activation or inhibition of inflammatory signaling and in the promotion of uncontrolled neuroinflammation with pathological consequences. MiR-155 is a pro-inflammatory mediator of the CNS and plays an important regulatory role. The purpose of this review is to summarize how miR-155 is regulated and the pathological consequences of its deregulation during neuroinflammatory disorders, including multiple sclerosis, Alzheimer’s disease and other neuroinflammatory disorders. Modulation of miRNAs’ expression could be used as a therapeutic strategy in the treatment of pathological neuroinflammation.


Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 210
Author(s):  
Aleksandra Swida-Barteczka ◽  
Zofia Szweykowska-Kulinska

MicroRNAs are short (19–24-nucleotide-long), non-coding RNA molecules. They downregulate gene expression by triggering the cleavage or translational inhibition of complementary mRNAs. Senescence is a stage of development following growth completion and is dependent on the expression of specific genes. MicroRNAs control the gene expression responsible for plant competence to answer senescence signals. Therefore, they coordinate the juvenile-to-adult phase transition of the whole plant, the growth and senescence phase of each leaf, age-related cellular structure changes during vessel formation, and remobilization of resources occurring during senescence. MicroRNAs are also engaged in the ripening and postharvest senescence of agronomically important fruits. Moreover, the hormonal regulation of senescence requires microRNA contribution. Environmental cues, such as darkness or drought, induce senescence-like processes in which microRNAs also play regulatory roles. In this review, we discuss recent findings concerning the role of microRNAs in the senescence of various plant species.


2014 ◽  
Vol 42 (6) ◽  
pp. 1629-1636 ◽  
Author(s):  
Jaimy Saif ◽  
Costanza Emanueli

miRNAs are highly conserved non-coding RNA molecules that negatively control gene expression by binding to target mRNAs promoting their degradation. A multitude of miRNAs have been reported to be involved in angiogenesis and vascular remodelling. In the present review, we aim to describe the effect of miRNAs in post-ischaemic repair. First, we describe the miRNAs reported in ischaemic diseases and in angiogenesis. Then we examine their capacity to modulate the behaviour of stem and progenitor cells which could be utilized for vascular repair. And finally we discuss the potential of miRNAs as new clinical biomarkers and therapeutic targets.


2020 ◽  
Vol 3 (4) ◽  
pp. e201900632
Author(s):  
Pavan Kumar Kakumani ◽  
Louis-Mathieu Harvey ◽  
François Houle ◽  
Tanit Guitart ◽  
Fátima Gebauer ◽  
...  

In animals, miRNAs are the most prevalent small non-coding RNA molecules controlling posttranscriptional gene regulation. The Argonaute proteins (AGO) mediate miRNA-guided gene silencing by recruiting multiple factors involved in translational repression, deadenylation, and decapping. Here, we report that CSDE1, an RNA-binding protein linked to stem cell maintenance and metastasis in cancer, interacts with AGO2 within miRNA-induced silencing complex and mediates gene silencing through its N-terminal domains. We show that CSDE1 interacts with LSM14A, a constituent of P-body assembly and further associates to the DCP1–DCP2 decapping complex, suggesting that CSDE1 could promote the decay of miRNA-induced silencing complex-targeted mRNAs. Together, our findings uncover a hitherto unknown mechanism used by CSDE1 in the control of gene expression mediated by the miRNA pathway.


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