scholarly journals tRNA fragments (tRFs) populations analysis in mutants affecting tRNAs processing and tRNA methylation

2019 ◽  
Author(s):  
Anahi Molla-Herman ◽  
Margarita Angelova ◽  
Clément Carré ◽  
Christophe Antoniewski ◽  
Jean-René Huynh
Keyword(s):  
Cell Types ◽  
Translation Control ◽  
Bioinformatic Pipeline ◽  
Transposon Silencing ◽  
Human Pathology ◽  
Analysis Workflow ◽  
Domains Of Life ◽  
Non Coding Rnas ◽  
Cell Proliferation Control ◽  
Nucleolar Rnas

AbstracttRNA fragments (tRFs) are a class of small non-coding RNAs (sncRNAs) derived from tRNAs. tRFs are highly abundant in many cell types including stem cells and cancer cells, and are found in all domains of life. Beyond translation control, tRFs have several functions ranging from transposon silencing to cell proliferation control. However, the analysis of tRFs presents specific challenges and their biogenesis is not well understood. They are very heterogeneous and highly modified by numerous post-transcriptional modifications. Here we describe a bioinformatic pipeline to study tRFs populations and shed light onto tRNA fragments biogenesis. Indeed, we used small RNAs Illumina sequencing datasets extracted from wild type and mutant Drosophila ovaries affecting two different highly conserved steps of tRNA biogenesis: 5’pre-tRNA processing (RNase-P subunit Rpp30) and tRNA 2’-O-methylation (CG7009 and CG5220). Using our pipeline, we show how defects in tRNA biogenesis affect nuclear and mitochondrial tRFs populations and other small non-coding RNAs biogenesis, such as small nucleolar RNAs (snoRNAs). This tRF analysis workflow will advance the current understanding of tRFs biogenesis, which is crucial to better comprehend tRFs roles and their implication in human pathology.

scholarly journals Emerging Data on the Diversity of Molecular Mechanisms Involving C/D snoRNAs

2021 ◽  
Vol 7 (2) ◽  
pp. 30
Author(s):  
Laeya Baldini ◽  
Bruno Charpentier ◽  
Stéphane Labialle
Keyword(s):  
Ribosomal Rna ◽  
Molecular Mechanisms ◽  
Molecular Level ◽  
Accurate Description ◽  
Small Nucleolar Rnas ◽  
Age Of Maturity ◽  
Non Coding Rnas ◽  
And Function ◽  
Nucleolar Rnas

Box C/D small nucleolar RNAs (C/D snoRNAs) represent an ancient family of small non-coding RNAs that are classically viewed as housekeeping guides for the 2′-O-methylation of ribosomal RNA in Archaea and Eukaryotes. However, an extensive set of studies now argues that they are involved in mechanisms that go well beyond this function. Here, we present these pieces of evidence in light of the current comprehension of the molecular mechanisms that control C/D snoRNA expression and function. From this inventory emerges that an accurate description of these activities at a molecular level is required to let the snoRNA field enter in a second age of maturity.

scholarly journals CALINCA—A Novel Pipeline for the Identification of lncRNAs in Podocyte Disease

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 692
Author(s):  
Sweta Talyan ◽  
Samantha Filipów ◽  
Michael Ignarski ◽  
Magdalena Smieszek ◽  
He Chen ◽  
...  
Keyword(s):  
Cell Biology ◽  
Mammalian Cells ◽  
De Novo ◽  
Depth Information ◽  
Gene Products ◽  
Classical Analysis ◽  
Protein Coding ◽  
Bioinformatic Pipeline ◽  
Non Coding Rnas ◽  
Filtration Unit

Diseases of the renal filtration unit—the glomerulus—are the most common cause of chronic kidney disease. Podocytes are the pivotal cell type for the function of this filter and focal-segmental glomerulosclerosis (FSGS) is a classic example of a podocytopathy leading to proteinuria and glomerular scarring. Currently, no targeted treatment of FSGS is available. This lack of therapeutic strategies is explained by a limited understanding of the defects in podocyte cell biology leading to FSGS. To date, most studies in the field have focused on protein-coding genes and their gene products. However, more than 80% of all transcripts produced by mammalian cells are actually non-coding. Here, long non-coding RNAs (lncRNAs) are a relatively novel class of transcripts and have not been systematically studied in FSGS to date. The appropriate tools to facilitate lncRNA research for the renal scientific community are urgently required due to a row of challenges compared to classical analysis pipelines optimized for coding RNA expression analysis. Here, we present the bioinformatic pipeline CALINCA as a solution for this problem. CALINCA automatically analyzes datasets from murine FSGS models and quantifies both annotated and de novo assembled lncRNAs. In addition, the tool provides in-depth information on podocyte specificity of these lncRNAs, as well as evolutionary conservation and expression in human datasets making this pipeline a crucial basis to lncRNA studies in FSGS.

scholarly journals Emerging Roles and Potential Applications of Non-Coding RNAs in Glioblastoma

2020 ◽  
Vol 21 (7) ◽  
pp. 2611 ◽  
Author(s):  
Carlos DeOcesano-Pereira ◽  
Raquel A. C. Machado ◽  
Ana Marisa Chudzinski-Tavassi ◽  
Mari Cleide Sogayar
Keyword(s):  
Cancer Type ◽  
Biological Processes ◽  
Small Nucleolar Rnas ◽  
Physiological Conditions ◽  
Master Regulators ◽  
Potential Applications ◽  
Non Coding Rnas ◽  
Regulatory Rnas ◽  
Nucleolar Rnas ◽  
Substantial Effort

Non-coding RNAs (ncRNAs) comprise a diversity of RNA species, which do not have the potential to encode proteins. Non-coding RNAs include two classes of RNAs, namely: short regulatory ncRNAs and long non-coding RNAs (lncRNAs). The short regulatory RNAs, containing up to 200 nucleotides, include small RNAs, such as microRNAs (miRNA), short interfering RNAs (siRNAs), piwi-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs). The lncRNAs include long antisense RNAs and long intergenic RNAs (lincRNAs). Non-coding RNAs have been implicated as master regulators of several biological processes, their expression being strictly regulated under physiological conditions. In recent years, particularly in the last decade, substantial effort has been made to investigate the function of ncRNAs in several human diseases, including cancer. Glioblastoma is the most common and aggressive type of brain cancer in adults, with deregulated expression of small and long ncRNAs having been implicated in onset, progression, invasiveness, and recurrence of this tumor. The aim of this review is to guide the reader through important aspects of miRNA and lncRNA biology, focusing on the molecular mechanism associated with the progression of this highly malignant cancer type.

Epigenetics of scleroderma: Integrating genetic, ethnic, age, and environmental effects

2019 ◽  
Vol 4 (3) ◽  
pp. 238-250 ◽  
Author(s):  
Paula S Ramos
Keyword(s):  
Systemic Sclerosis ◽  
Epigenetic Regulation ◽  
Environmental Effects ◽  
Genetic Factors ◽  
Cell Types ◽  
Underlying Mechanism ◽  
Epigenome Editing ◽  
Non Coding Rnas ◽  
Epigenetic Editing

Scleroderma or systemic sclerosis is thought to result from the interplay between environmental or non-genetic factors in a genetically susceptible individual. Epigenetic modifications are influenced by genetic variation and environmental exposures, and change with chronological age and between populations. Despite progress in identifying genetic, epigenetic, and environmental risk factors, the underlying mechanism of systemic sclerosis remains unclear. Since epigenetics provides the regulatory mechanism linking genetic and non-genetic factors to gene expression, understanding the role of epigenetic regulation in systemic sclerosis will elucidate how these factors interact to cause systemic sclerosis. Among the cell types under tight epigenetic control and susceptible to epigenetic dysregulation, immune cells are critically involved in early pathogenic events in the progression of fibrosis and systemic sclerosis. This review starts by summarizing the changes in DNA methylation, histone modification, and non-coding RNAs associated with systemic sclerosis. It then discusses the role of genetic, ethnic, age, and environmental effects on epigenetic regulation, with a focus on immune system dysregulation. Given the potential of epigenome editing technologies for cell reprogramming and as a therapeutic approach for durable gene regulation, this review concludes with a prospect on epigenetic editing. Although epigenomics in systemic sclerosis is in its infancy, future studies will help elucidate the regulatory mechanisms underpinning systemic sclerosis and inform the design of targeted epigenetic therapies to control its dysregulation.

scholarly journals Epigenetic Regulation of the Hippocampus, with Special Reference to Radiation Exposure

2020 ◽  
Vol 21 (24) ◽  
pp. 9514
Author(s):  
Genevieve Saw ◽  
Feng Ru Tang
Keyword(s):  
Epigenetic Regulation ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Epigenetic Changes ◽  
Epigenetic Factors ◽  
Hippocampal Function ◽  
Neuropsychological Disorders ◽  
Radiation Induced ◽  
Non Coding Rnas ◽  
And Function

The hippocampus is crucial in learning, memory and emotion processing, and is involved in the development of different neurological and neuropsychological disorders. Several epigenetic factors, including DNA methylation, histone modifications and non-coding RNAs, have been shown to regulate the development and function of the hippocampus, and the alteration of epigenetic regulation may play important roles in the development of neurocognitive and neurodegenerative diseases. This review summarizes the epigenetic modifications of various cell types and processes within the hippocampus and their resulting effects on cognition, memory and overall hippocampal function. In addition, the effects of exposure to radiation that may induce a myriad of epigenetic changes in the hippocampus are reviewed. By assessing and evaluating the current literature, we hope to prompt a more thorough understanding of the molecular mechanisms that underlie radiation-induced epigenetic changes, an area which can be further explored.

scholarly journals Non-coding RNAs in cardiovascular cell biology and atherosclerosis

2019 ◽  
Vol 115 (12) ◽  
pp. 1732-1756 ◽  
Author(s):  
Francesca Fasolo ◽  
Karina Di Gregoli ◽  
Lars Maegdefessel ◽  
Jason L Johnson
Keyword(s):  
Animal Models ◽  
Cell Biology ◽  
Therapeutic Targets ◽  
Cell Types ◽  
In Vivo Studies ◽  
Circular Rnas ◽  
Potential Contribution ◽  
Clinicopathological Findings ◽  
Non Coding Rnas

Abstract Atherosclerosis underlies the predominant number of cardiovascular diseases and remains a leading cause of morbidity and mortality worldwide. The development, progression and formation of clinically relevant atherosclerotic plaques involves the interaction of distinct and over-lapping mechanisms which dictate the roles and actions of multiple resident and recruited cell types including endothelial cells, vascular smooth muscle cells, and monocyte/macrophages. The discovery of non-coding RNAs (ncRNAs) including microRNAs, long non-coding RNAs, and circular RNAs, and their identification as key mechanistic regulators of mRNA and protein expression has piqued interest in their potential contribution to atherosclerosis. Accruing evidence has revealed ncRNAs regulate pivotal cellular and molecular processes during all stages of atherosclerosis including cell invasion, growth, and survival; cellular uptake and efflux of lipids, expression and release of pro- and anti-inflammatory intermediaries, and proteolytic balance. The expression profile of ncRNAs within atherosclerotic lesions and the circulation have been determined with the aim of identifying individual or clusters of ncRNAs which may be viable therapeutic targets alongside deployment as biomarkers of atherosclerotic plaque progression. Consequently, numerous in vivo studies have been convened to determine the effects of moderating the function or expression of select ncRNAs in well-characterized animal models of atherosclerosis. Together, clinicopathological findings and studies in animal models have elucidated the multifaceted and frequently divergent effects ncRNAs impose both directly and indirectly on the formation and progression of atherosclerosis. From these findings’ potential novel therapeutic targets and strategies have been discovered which may pave the way for further translational studies and possibly taken forward for clinical application.

scholarly journals MicroRNA-301a inhibition enhances the immunomodulatory functions of adipose-derived mesenchymal stem cells by induction of macrophage M2 polarization

2020 ◽  
Vol 34 ◽  
pp. 205873842096609
Author(s):  
Li-Wen Hsu ◽  
Kuang-Tzu Huang ◽  
Toshiaki Nakano ◽  
King-Wah Chiu ◽  
Kuang-Den Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Macrophage Polarization ◽  
Cell Types ◽  
Prostaglandin E ◽  
M2 Macrophage ◽  
Toll Like Receptor ◽  
Arginase 1 ◽  
Pge2 Concentration ◽  
Non Coding Rnas

MicroRNAs (miRNAs) are a class of short non-coding RNAs that play a significant role in biological processes in various cell types, including mesenchymal stem cells (MSCs). However, how miRNAs regulate the immunomodulatory functions of adipose-derived MSCs (AD-MSCs) remains unknown. Here, we showed that modulation of miR-301a in AD-MSCs altered macrophage polarization. Bone marrow (BM)-derived macrophages were stimulated with LPS (1 μg/ml) and co-cultured with miRNA transfected AD-MSCs for 24 h. The expression of M1 and M2 markers in macrophages was analyzed. Inhibition of miR-301a induced M2 macrophage with arginase-1, CD163, CD206, and IL-10 upregulation. Additionally, toll-like receptor (TLR)-4 mRNA expression in macrophages was downregulated in co-cultures with AD-MSCs transfected with a miR-301a inhibitor. Nitric oxide (NO) in the supernatant of AD-MSC/macrophage co-culture was also suppressed by inhibition of miR-301a in AD-MSCs. We further found that suppression of miR-301a in AD-MSCs increased prostaglandin E2 (PGE2) concentration in the conditioned medium of the co-culture. Taken together, the results of our study indicate that miR-301a can modulate the immunoregulatory functions of AD-MSCs that favor the applicability as a potential immunotherapeutic agent.

scholarly journals Assembly and Function of Gonad-Specific Non-Membranous Organelles in Drosophila piRNA Biogenesis

2019 ◽  
Vol 5 (4) ◽  
pp. 52 ◽  
Author(s):  
Shigeki Hirakata ◽  
Mikiko C. Siomi
Keyword(s):  
Dna Damage ◽  
Gonadal Development ◽  
Mitochondrial Membranes ◽  
Animal Life ◽  
Transposon Silencing ◽  
Dna Elements ◽  
Non Coding Rnas ◽  
And Function ◽  
Pirna Pathway

PIWI-interacting RNAs (piRNAs) are small non-coding RNAs that repress transposons in animal germlines. This protects the genome from the invasive DNA elements. piRNA pathway failures lead to DNA damage, gonadal development defects, and infertility. Thus, the piRNA pathway is indispensable for the continuation of animal life. piRNA-mediated transposon silencing occurs in both the nucleus and cytoplasm while piRNA biogenesis is a solely cytoplasmic event. piRNA production requires a number of proteins, the majority of which localize to non-membranous organelles that specifically appear in the gonads. Other piRNA factors are localized on outer mitochondrial membranes. In situ RNA hybridization experiments show that piRNA precursors are compartmentalized into other non-membranous organelles. In this review, we summarize recent findings about the function of these organelles in the Drosophila piRNA pathway by focusing on their assembly and function.

scholarly journals PIWI proteins and their interactors in piRNA biogenesis, germline development and gene expression

2014 ◽  
Vol 1 (2) ◽  
pp. 205-218 ◽  
Author(s):  
Hsueh-Yen Ku ◽  
Haifan Lin
Keyword(s):  
Translational Control ◽  
Mrna Turnover ◽  
Regulatory Function ◽  
Piwi Protein ◽  
Germline Development ◽  
Epigenetic Programming ◽  
Transposon Silencing ◽  
Tudor Domain ◽  
Argonaute Family ◽  
Non Coding Rnas

Abstract PIWI-interacting RNAs (piRNAs) are a complex class of small non-coding RNAs that are mostly 24–32 nucleotides in length and composed of at least hundreds of thousands of species that specifically interact with the PIWI protein subfamily of the ARGONAUTE family. Recent studies revealed that PIWI proteins interact with a number of proteins, especially the TUDOR-domain-containing proteins, to regulate piRNA biogenesis and regulatory function. Current research also provides evidence that PIWI proteins and piRNAs are not only crucial for transposon silencing in the germline, but also mediate novel mechanisms of epigenetic programming, DNA rearrangements, mRNA turnover, and translational control both in the germline and in the soma. These new discoveries begin to reveal an exciting new dimension of gene regulation in the cell.

piRNA identification based on motif discovery

2014 ◽  
Vol 10 (12) ◽  
pp. 3075-3080 ◽  
Author(s):  
Xiuqin Liu ◽  
Jun Ding ◽  
Fuzhou Gong
Keyword(s):  
Epigenetic Regulation ◽  
Motif Discovery ◽  
Germline Development ◽  
Transposon Silencing ◽  
Non Coding Rnas

Piwi-interacting RNA (piRNA) is a class of small non-coding RNAs about 24 to 32 nucleotides long, associated with PIWI proteins, which are involved in germline development, transposon silencing, and epigenetic regulation.

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