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CNS & Neurological Disorders Drug... 2015MicroRNAs (miRNAs) are ~22 nucleotide non-coding RNAs that control gene expression post-transcriptionally by base pairing to mRNAs. MiRNAs are predicted to target ~50%... (Review)
Review
MicroRNAs (miRNAs) are ~22 nucleotide non-coding RNAs that control gene expression post-transcriptionally by base pairing to mRNAs. MiRNAs are predicted to target ~50% of all protein-coding genes and functional studies indicate that they participate in the regulation of almost every cellular process. They also play a key role in pathogenetic mechanisms underlying several diseases, e.g. cancer, cardiovascular diseases, autoimmune diseases, and neurodegenerative diseases. Several miRNAs are expressed in the human brain where they contribute to equilibrium between maintenance and differentiation of neural stem cells. MiRNAs specific mechanisms of action and their roles in brain development and synaptic plasticity resulted in a great interest in the analysis of their potential role in the pathogenesis and pathophysiology of neuropsychiatric disorders. Currently, schizophrenia is one of the fields in psychiatry where miRNAs have been most widely investigated. The understanding of miRNAs role in schizophrenia has been achieved through association, functional and expression profiling studies on post mortem brain and peripheral tissues. Several studies identified association between neuropsychiatric disorders and variants in miRNAs including variations in miRNA/primary-/precursor-miRNAs sequences, in miRNAs biogenesis machinery genes, in the 3'UTR of target genes and in miRNAs expression. In summary, there is growing evidence that miRNAs exert a crucial role in gene expression regulation in the central nervous system and are altered in the development, presentation and response to treatment of psychiatric disorders. In this review we summarize the most significant results of experimental studies aimed at highlighting the involvement of human miRNAs in schizophrenia.
Topics: Animals; Humans; MicroRNAs; Schizophrenia
PubMed: 25613509
DOI: 10.2174/1871527314666150116124253 -
International Journal of Molecular... Jun 2016Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents, but its pathogenesis has been difficult to establish because of its well-known... (Review)
Review
Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents, but its pathogenesis has been difficult to establish because of its well-known heterogeneous nature. OS has been associated with genetic and cytogenetic abnormalities, which include function-impairing mutations in tumor suppressors and the activation of oncogenes. OS tumorigenesis has been linked to alterations of several genes characterized by a high level of genetic instability and recurrent DNA amplifications and deletions. MicroRNAs (miRNAs), 18-25-nucleotide noncoding RNAs, are critical for various biological processes like differentiation, cell growth and cell death. Dysregulation of miRNA expression leads to phenotypic and genotypic changes in cells, which leads to cancer. Studies on miRNAs have initiated a significant effect in both diagnosis and treatment of cancer. This review focuses on the current knowledge of clinical applications of miRNAs for the better diagnosis and management of OS.
Topics: Animals; Biomarkers; Bone Neoplasms; Cell Transformation, Neoplastic; Gene Expression Regulation, Neoplastic; Genetic Therapy; Humans; MicroRNAs; Osteosarcoma; RNA Interference; RNA, Messenger
PubMed: 27271607
DOI: 10.3390/ijms17060877 -
Wiley Interdisciplinary Reviews. RNA Mar 2023An important proportion of microRNA (miRNA) genes tend to lie close to each other within animal genomes. Such genomic organization is generally referred to as miRNA... (Review)
Review
An important proportion of microRNA (miRNA) genes tend to lie close to each other within animal genomes. Such genomic organization is generally referred to as miRNA clusters. Even though many miRNA clusters have been greatly studied, most attention has been usually focused on functional impacts of clustered miRNA co-expression. However, there is also another compelling aspect about these miRNA clusters, their polycistronic nature. Being transcribed on a single RNA precursor, polycistronic miRNAs benefit from common transcriptional regulation allowing their coordinated expression. And yet, numerous reports have revealed striking discrepancies in the accumulation of mature miRNAs produced from the same cluster. Indeed, the larger polycistronic transcripts can act as platforms providing unforeseen post-transcriptional regulatory mechanisms controlling individual miRNA processing, thus leading to differential miRNA expression, and sometimes even challenging the general assumption that polycistronic miRNAs are co-expressed. In this review, we aim to address the current knowledge about how miRNA polycistrons are post-transcriptionally regulated. In particular, we will focus on the mechanisms occurring at the level of the primary transcript, which are highly relevant for individual miRNA processing and as such have a direct repercussion on miRNA function within the cell. This article is categorized under: RNA Processing > Processing of Small RNAs Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.
Topics: Animals; MicroRNAs; Gene Expression Regulation; RNA Processing, Post-Transcriptional; RNA Interference
PubMed: 35702737
DOI: 10.1002/wrna.1749 -
Methods in Molecular Biology (Clifton,... 2021MicroRNAs control plant development and are key regulators of plant responses to biotic and abiotic stresses. Thus, their expression must be carefully controlled since...
MicroRNAs control plant development and are key regulators of plant responses to biotic and abiotic stresses. Thus, their expression must be carefully controlled since both excess and deficiency of a given microRNA may be deleterious to plant cell. MicroRNA expression regulation can occur at several stages of their biogenesis pathway. One of the most important of these regulatory checkpoints is transcription efficiency. mirEX database is a tool for exploration and visualization of plant pri-miRNA expression profiles. It includes results obtained using high-throughput RT-qPCR platform designed to monitor pri-miRNA expression in different miRNA biogenesis mutants and developmental stages of Arabidopsis, barley, and Pellia plants. A step-by-step instruction for browsing the database and detailed protocol for high-throughput RT-qPCR experiments, including list of primers designed for the amplification of pri-miRNAs, are presented.
Topics: Arabidopsis; Gene Expression Regulation, Plant; Hordeum; MicroRNAs
PubMed: 32797451
DOI: 10.1007/978-1-0716-0743-5_5 -
Genes & Development Dec 2004RNase III proteins play key roles in microRNA (miRNA) biogenesis. The nuclear RNase III Drosha cleaves primary miRNAs (pri-miRNAs) to release hairpin-shaped pre-miRNAs... (Comparative Study)
Comparative Study
RNase III proteins play key roles in microRNA (miRNA) biogenesis. The nuclear RNase III Drosha cleaves primary miRNAs (pri-miRNAs) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic RNase III Dicer to generate mature miRNAs. While Dicer (class III) and other simple RNase III proteins (class I) have been studied intensively, the class II enzyme Drosha remains to be characterized. Here we dissected the action mechanism of human Drosha by generating mutants and by characterizing its new interacting partner, DGCR8. The basic action mechanism of Drosha was found to be similar to that of human Dicer; the RNase III domains A and B form an intramolecular dimer and cleave the 3' and 5' strands of the stem, respectively. Human Drosha fractionates at approximately 650 kDa, indicating that Drosha functions as a large complex. In this complex, Drosha interacts with DGCR8, which contains two double-stranded RNA (dsRNA)-binding domains. By RNAi and biochemical reconstitution, we show that DGCR8 may be an essential component of the pri-miRNA processing complex, along with Drosha. Based on these results, we propose a model for the action mechanism of class II RNase III proteins.
Topics: Blotting, Northern; Blotting, Western; Cells, Cultured; Chromatography, Gel; DNA Primers; Humans; Immunoprecipitation; Mass Spectrometry; MicroRNAs; Models, Biological; Mutagenesis, Site-Directed; Proteins; RNA Interference; RNA Precursors; RNA Processing, Post-Transcriptional; RNA-Binding Proteins; Reverse Transcriptase Polymerase Chain Reaction; Ribonuclease III
PubMed: 15574589
DOI: 10.1101/gad.1262504 -
Biochimie Jul 2023Couch's spadefoot toad (Scaphiopus couchii) spends most of the year underground in a hypometabolic state known as estivation. During this time, they overcome significant...
Couch's spadefoot toad (Scaphiopus couchii) spends most of the year underground in a hypometabolic state known as estivation. During this time, they overcome significant dehydration and lack of food through many mechanisms including employing metabolic rate depression (MRD), increasing urea concentration, switching to lipid oxidation as the primary energy source, and decreasing their breathing and heart rate. MicroRNA (miRNA) are known to regulate translation by targeting messenger RNA (mRNA) for degradation or temporary storage, with several studies having reported that miRNA is differentially expressed during MRD, including estivation. Thus, we hypothesized that miRNA would be involved in gene regulation during estivation in S. couchii heart. Next-generation sequencing and bioinformatic analyses were used to assess changes in miRNA expression in response to two-month estivation and to predict the downstream effects of this expression. KEGG and GO analyses indicated that ribosome and cardiac muscle contraction are among the pathways predicted to be upregulated, whereas cell signaling and fatty acid metabolism were predicted to be downregulated. Together these results suggest that miRNAs contribute to the regulation of gene expression related to cardiac muscle physiology and energy metabolism during estivation.
Topics: Animals; Estivation; Anura; MicroRNAs
PubMed: 36627041
DOI: 10.1016/j.biochi.2023.01.001 -
Current Biology : CB Jan 2005The ribonuclease Drosha requires a dedicated double-stranded RNA binding protein to convert long, nuclear primary microRNA transcripts into shorter pre-microRNA... (Review)
Review
The ribonuclease Drosha requires a dedicated double-stranded RNA binding protein to convert long, nuclear primary microRNA transcripts into shorter pre-microRNA stem-loops, the cytoplasmic precursors from which mature microRNAs are ultimately excised.
Topics: Animals; Gene Expression Regulation; Humans; MicroRNAs; Proteins; RNA-Binding Proteins; Ribonuclease III
PubMed: 15668159
DOI: 10.1016/j.cub.2004.12.057 -
International Journal of Molecular... Jan 2023This review aims to consider retrospectively the available data on the coding properties of pri-microRNAs and the regulatory functions of their open reading frames... (Review)
Review
This review aims to consider retrospectively the available data on the coding properties of pri-microRNAs and the regulatory functions of their open reading frames (ORFs) and the encoded peptides (miPEPs). Studies identifying miPEPs and analyzing the fine molecular mechanisms of their functional activities are reviewed together with a brief description of the methods to identify pri-miRNA ORFs and the encoded protein products. Generally, miPEPs have been identified in many plant species of several families and in a few animal species. Importantly, molecular mechanisms of the miPEP action are often quite different between flowering plants and metazoan species. Requirement for the additional studies in these directions is highlighted by alternative findings concerning negative or positive regulation of pri-miRNA/miRNA expression by miPEPs in plants and animals. Additionally, the question of how miPEPs are distributed in non-flowering plant taxa is very important for understanding the evolutionary origin of such micropeptides. Evidently, further extensive studies are needed to explore the functions of miPEPs and the corresponding ORFs and to understand the full set of their roles in eukaryotic organisms. Thus, we address the most recent integrative views of different genomic, physiological, and molecular aspects concerning the expression of miPEPs and their possible fine functions.
Topics: Animals; MicroRNAs; Open Reading Frames; Retrospective Studies; Plants; Micropeptides
PubMed: 36768436
DOI: 10.3390/ijms24032114 -
Circulation Research Jan 2014
Topics: Animals; Cell Movement; Cell Proliferation; Familial Primary Pulmonary Hypertension; Female; Fibroblasts; Humans; Hypertension, Pulmonary; Male; MicroRNAs
PubMed: 24385500
DOI: 10.1161/CIRCRESAHA.113.302838 -
Free Radical Biology & Medicine Sep 2013Hypoxia, or low oxygen tension, is a unique environmental stress that induces global changes in a complex regulatory network of transcription factors and signaling... (Review)
Review
Hypoxia, or low oxygen tension, is a unique environmental stress that induces global changes in a complex regulatory network of transcription factors and signaling proteins to coordinate cellular adaptations in metabolism, proliferation, DNA repair, and apoptosis. Several lines of evidence now establish microRNAs (miRNAs), which are short noncoding RNAs that regulate gene expression through posttranscriptional mechanisms, as key elements in this response to hypoxia. Oxygen deprivation induces a distinct shift in the expression of a specific group of miRNAs, termed hypoxamirs, and emerging evidence indicates that hypoxia regulates several facets of hypoxamir transcription, maturation, and function. Transcription factors such as hypoxia-inducible factor are upregulated under conditions of low oxygen availability and directly activate the transcription of a subset of hypoxamirs. Conversely, hypoxia selectively represses other hypoxamirs through less well characterized mechanisms. In addition, oxygen deprivation has been directly implicated in epigenetic modifications such as DNA demethylation that control specific miRNA transcription. Finally, hypoxia also modulates the activity of key proteins that control posttranscriptional events in the maturation and activity of miRNAs. Collectively, these findings establish hypoxia as an important proximal regulator of miRNA biogenesis and function. It will be important for future studies to address the relative contributions of transcriptional and posttranscriptional events in the regulation of specific hypoxamirs and how such miRNAs are coordinated in order to integrate into the complex hierarchical regulatory network induced by hypoxia.
Topics: Adaptation, Physiological; Animals; Apoptosis; Epigenesis, Genetic; Gene Expression Regulation; Humans; Hypoxia; MicroRNAs; Oxygen; Signal Transduction; Transcription Factors; Transcription, Genetic
PubMed: 23712003
DOI: 10.1016/j.freeradbiomed.2013.05.022