scholarly journals Deciphering the tRNA-derived small RNAs: origin, development, and future

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Bowen Liu ◽  
Jinling Cao ◽  
Xiangyun Wang ◽  
Chunlei Guo ◽  
Yunxia Liu ◽  
...  
Keyword(s):  
Subcellular Localization ◽  
Small Rnas ◽  
Molecular Mechanisms ◽  
Noncoding Rnas ◽  
Transfer Rna ◽  
Action Mechanism ◽  
Chemical Modifications ◽  
Future Directions ◽  
Small Noncoding Rnas ◽  
New Biomarkers

AbstractTransfer RNA (tRNA)-derived small RNAs (tsRNAs), a novel category of small noncoding RNAs, are enzymatically cleaved from tRNAs. Previous reports have shed some light on the roles of tsRNAs in the development of human diseases. However, our knowledge about tsRNAs is still relatively lacking. In this paper, we review the biogenesis, classification, subcellular localization as well as action mechanism of tsRNAs, and discuss the association between chemical modifications of tRNAs and the production and functions of tsRNAs. Furthermore, using immunity, metabolism, and malignancy as examples, we summarize the molecular mechanisms of tsRNAs in diseases and evaluate the potential of tsRNAs as new biomarkers and therapeutic targets. At the same time, we compile and introduce several resource databases that are currently publicly available for analyzing tsRNAs. Finally, we discuss the challenges associated with research in this field and future directions.

scholarly journals Dysregulation of a family of short noncoding RNAs, tsRNAs, in human cancer

2016 ◽  
Vol 113 (18) ◽  
pp. 5071-5076 ◽  
Author(s):  
Yuri Pekarsky ◽  
Veronica Balatti ◽  
Alexey Palamarchuk ◽  
Lara Rizzotto ◽  
Dario Veneziano ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Rnas ◽  
Northern Blot Analysis ◽  
Human Cancer ◽  
Noncoding Rnas ◽  
Lymphocytic Leukemia ◽  
P Element ◽  
Human Leukemia ◽  
Hematopoietic Malignancies ◽  
Small Noncoding Rnas

Chronic lymphocytic leukemia (CLL) is the most common human leukemia, and transgenic mouse studies indicate that activation of the T-cell leukemia/lymphoma 1 (TCL1) oncogene is a contributing event in the pathogenesis of the aggressive form of this disease. While studying the regulation of TCL1 expression, we identified the microRNA cluster miR-4521/3676 and discovered that these two microRNAs are associated with tRNA sequences and that this region can produce two small RNAs, members of a recently identified class of small noncoding RNAs, tRNA-derived small RNAs (tsRNAs). We further proved that miR-3676 and miR-4521 are tsRNAs using Northern blot analysis. We found that, like ts-3676, ts-4521 is down-regulated and mutated in CLL. Analysis of lung cancer samples revealed that both ts-3676 and ts-4521 are down-regulated and mutated in patient tumor samples. Because tsRNAs are similar in nature to piRNAs [P-element–induced wimpy testis (Piwi)-interacting small RNAs], we investigated whether ts-3676 and ts-4521 can interact with Piwi proteins and found these two tsRNAs in complexes containing Piwi-like protein 2 (PIWIL2). To determine whether other tsRNAs are involved in cancer, we generated a custom microarray chip containing 120 tsRNAs 16 bp or more in size. Microarray hybridization experiments revealed tsRNA signatures in CLL and lung cancer, indicating that, like microRNAs, tsRNAs may have an oncogenic and/or tumor-suppressor function in hematopoietic malignancies and solid tumors. Thus, our results show that tsRNAs are dysregulated in human cancer.

scholarly journals Use of miRNAs as Biomarkers in Sepsis

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Raluca Dumache ◽  
Alexandru Florin Rogobete ◽  
Ovidiu Horea Bedreag ◽  
Mirela Sarandan ◽  
Alina Carmen Cradigati ◽  
...  
Keyword(s):  
Causes Of Death ◽  
Noncoding Rnas ◽  
Circulating Mirnas ◽  
Small Noncoding Rnas ◽  
Stable Species ◽  
Common Causes ◽  
Critical Patients ◽  
New Biomarkers ◽  
Potential Biomarkers

Sepsis is one of the most common causes of death in critical patients. Severe generalized inflammation, infections, and severe physiological imbalances significantly decrease the survival rate with more than 50%. Moreover, monitoring, evaluation, and therapy management often become extremely difficult for the clinician in this type of patients. Current methods of diagnosing sepsis vary based especially on the determination of biochemical-humoral markers, such as cytokines, components of the complement, and proinflammatory and anti-inflammatory compounds. Recent studies highlight the use of new biomarkers for sepsis, namely, miRNAs. miRNAs belong to a class of small, noncoding RNAs with an approximate content of 19–23 nucleotides. Following biochemical and physiological imbalances, the expression of miRNAs in blood or other body fluids changes significantly. Moreover, its stability, specificity, and selectivity make miRNAs ideal candidates for sepsis biomarkers. In conclusion, we can affirm that stable species of circulating miRNAs represent potential biomarkers for monitoring the evolution of sepsis.

scholarly journals MicroRNAs’ Involvement in Osteoarthritis and the Prospects for Treatments

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Xiao-Ming Yu ◽  
Hao-Ye Meng ◽  
Xue-Ling Yuan ◽  
Yu Wang ◽  
Quan-Yi Guo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Noncoding Rnas ◽  
Genetic Changes ◽  
Future Studies ◽  
Small Noncoding Rnas ◽  
Cartilage Homeostasis ◽  
Target Binding ◽  
And Cartilage

Osteoarthritis (OA) is a chronic disease and its etiology is complex. With increasing OA incidence, more and more people are facing heavy financial and social burdens from the disease. Genetics-related aspects of OA pathogenesis are not well understood. Recent reports have examined the molecular mechanisms and genes related to OA. It has been realized that genetic changes in articular cartilage and bone may contribute to OA’s development. Osteoclasts, osteoblasts, osteocytes, and chondrocytes in joints must express appropriate genes to achieve tissue homeostasis, and errors in this can cause OA. MicroRNAs (miRNAs) are small noncoding RNAs that have been discovered to be overarching regulators of gene expression. Their ability to repress many target genes and their target-binding specificity indicate a complex network of interactions, which is still being defined. Many studies have focused on the role of miRNAs in bone and cartilage and have identified numbers of miRNAs that play important roles in regulating bone and cartilage homeostasis. Those miRNAs may also be involved in the pathology of OA, which is the focus of this review. Future studies on the role of miRNAs in OA will provide important clues leading to a better understanding of the mechanism(s) of OA and, more particularly, to the development of therapeutic targets for OA.

scholarly journals MicroRNA Profiling in Cartilage Ageing

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Panagiotis Balaskas ◽  
Katarzyna Goljanek-Whysall ◽  
Peter Clegg ◽  
Yongxiang Fang ◽  
Andy Cremers ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Noncoding Rnas ◽  
Therapeutic Targets ◽  
Small Noncoding Rnas ◽  
Microarray Study ◽  
Age Related ◽  
Differentially Expressed Mirnas ◽  
Joint Disorder ◽  
Age Related Changes ◽  
Independent Cohort

Osteoarthritis (OA) is the most common age-related joint disorder in man. MicroRNAs (miRNA), a class of small noncoding RNAs, are potential therapeutic targets for regulating molecular mechanisms in both disease and ageing. Whilst there is an increasing amount of research on the roles of miRNAs in ageing, there has been scant research on age-related changes in miRNA in a cartilage. We undertook a microarray study on young and old human cartilages. Findings were validated in an independent cohort. Contrasts between these samples identified twenty differentially expressed miRNAs in a cartilage from old donors, derived from an OA environment which clustered based on OA severity. We identified a number of recognised and novel miRNAs changing in cartilage ageing and OA including miR-126: a potential new candidate with a role in OA pathogenesis. These analyses represent important candidates that have the potential as cartilage ageing and OA biomarkers and therapeutic targets.

scholarly journals Small RNA Mobility: Spread of RNA Silencing Effectors and its Effect on Developmental Processes and Stress Adaptation in Plants

2019 ◽  
Vol 20 (17) ◽  
pp. 4306 ◽  
Author(s):  
Chiara Pagliarani ◽  
Giorgio Gambino
Keyword(s):  
Small Rnas ◽  
Rna Silencing ◽  
Physiological Responses ◽  
Noncoding Rnas ◽  
Environmental Cues ◽  
Physiological Changes ◽  
Abiotic And Biotic Stresses ◽  
Biotic Stresses ◽  
Small Noncoding Rnas ◽  
Surrounding Environment

Plants are exposed every day to multiple environmental cues, and tight transcriptome reprogramming is necessary to control the balance between responses to stress and processes of plant growth. In this context, the silencing phenomena mediated by small RNAs can drive transcriptional and epigenetic regulatory modifications, in turn shaping plant development and adaptation to the surrounding environment. Mounting experimental evidence has recently pointed to small noncoding RNAs as fundamental players in molecular signalling cascades activated upon exposure to abiotic and biotic stresses. Although, in the last decade, studies on stress responsive small RNAs increased significantly in many plant species, the physiological responses triggered by these molecules in the presence of environmental stresses need to be further explored. It is noteworthy that small RNAs can move either cell-to-cell or systemically, thus acting as mobile silencing effectors within the plant. This aspect has great importance when physiological changes, as well as epigenetic regulatory marks, are inspected in light of plant environmental adaptation. In this review, we provide an overview of the categories of mobile small RNAs in plants, particularly focusing on the biological implications of non-cell autonomous RNA silencing in the stress adaptive response and epigenetic modifications.

scholarly journals Visualization of the small RNA transcriptome using seqclusterViz

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 232 ◽  
Author(s):  
Lorena Pantano ◽  
Francisco Pantano ◽  
Eulalia Marti ◽  
Shannan Ho Sui
Keyword(s):  
Gene Regulation ◽  
Small Rna ◽  
Small Rnas ◽  
Noncoding Rnas ◽  
Model Organisms ◽  
Visualization Tool ◽  
Rna Seq ◽  
Small Noncoding Rnas ◽  
Different Types ◽  
Genomic Locations

The study of small RNAs provides us with a deeper understanding of the complexity of gene regulation within cells. Of the different types of small RNAs, the most important in mammals are miRNA, tRNA fragments and piRNAs. Using small RNA-seq analysis, we can study all small RNA types simultaneously, with the potential to detect novel small RNA types. We describe SeqclusterViz, an interactive HTML-javascript webpage for visualizing small noncoding RNAs (small RNAs) detected by Seqcluster. The SeqclusterViz tool allows users to visualize known and novel small RNA types in model or non-model organisms, and to select small RNA candidates for further validation. SeqclusterViz is divided into three panels: i) query-ready tables showing detected small RNA clusters and their genomic locations, ii) the expression profile over the precursor for all the samples together with RNA secondary structures, and iii) the mostly highly expressed sequences. Here, we show the capabilities of the visualization tool and its validation using human brain samples from patients with Parkinson’s disease.

scholarly journals Visualization of the small RNA transcriptome using seqclusterViz

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 232
Author(s):  
Lorena Pantano ◽  
Francisco Pantano ◽  
Eulalia Marti ◽  
Shannan Ho Sui
Keyword(s):  
Gene Regulation ◽  
Small Rna ◽  
Small Rnas ◽  
Noncoding Rnas ◽  
Model Organisms ◽  
Visualization Tool ◽  
Rna Seq ◽  
Small Noncoding Rnas ◽  
Different Types ◽  
Genomic Locations

The study of small RNAs provides us with a deeper understanding of the complexity of gene regulation within cells. Of the different types of small RNAs, the most important in mammals are miRNA, tRNA fragments and piRNAs. Using small RNA-seq analysis, we can study all small RNA types simultaneously, with the potential to detect novel small RNA types. We describe SeqclusterViz, an interactive HTML-javascript webpage for visualizing small noncoding RNAs (small RNAs) detected by Seqcluster. The SeqclusterViz tool allows users to visualize known and novel small RNA types in model or non-model organisms, and to select small RNA candidates for further validation. SeqclusterViz is divided into three panels: i) query-ready tables showing detected small RNA clusters and their genomic locations, ii) the expression profile over the precursor for all the samples together with RNA secondary structures, and iii) the mostly highly expressed sequences. Here, we show the capabilities of the visualization tool and its validation using human brain samples from patients with Parkinson’s disease .

scholarly journals Exosomal miRNAs in Heart Disease

Physiology ◽  
2016 ◽  
Vol 31 (1) ◽  
pp. 16-24 ◽  
Author(s):  
Claudio Iaconetti ◽  
Sabato Sorrentino ◽  
Salvatore De Rosa ◽  
Ciro Indolfi
Keyword(s):  
Heart Disease ◽  
Posttranscriptional Regulation ◽  
Functional Role ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Small Noncoding Rnas ◽  
Micro Rnas ◽  
Exosomal Mirnas ◽  
New Biomarkers ◽  
Potential Use

Micro-RNAs (miRNAs) are small noncoding RNAs involved in the posttranscriptional regulation of gene expression. Exosomes have recently emerged as novel elements of intercellular communication in the cardiovascular system. Exosomal miRNAs could be key players in intercellular cross-talk, particularly during different diseases such as myocardial infarction (MI) and heart failure (HF). This review addresses the functional role played by exosomal miRNAs in heart disease and their potential use as new biomarkers.

scholarly journals MicroRNAs as Biomarkers for Early Diagnosis, Prognosis, and Therapeutic Targeting of Ovarian Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-25
Author(s):  
Yegane Mirahmadi ◽  
Reza Nabavi ◽  
Fourough Taheri ◽  
Mohammad Mahdi Samadian ◽  
Zari Naderi Ghale-Noie ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Diagnosis ◽  
Molecular Mechanisms ◽  
Gynecologic Cancer ◽  
Small Noncoding Rnas ◽  
Human Cancers ◽  
Mrna Targets ◽  
Interesting Approach ◽  
New Biomarkers

Ovarian cancer is the major cause of gynecologic cancer-related mortality. Regardless of outstanding advances, which have been made for improving the prognosis, diagnosis, and treatment of ovarian cancer, the majority of the patients will die of the disease. Late-stage diagnosis and the occurrence of recurrent cancer after treatment are the most important causes of the high mortality rate observed in ovarian cancer patients. Unraveling the molecular mechanisms involved in the pathogenesis of ovarian cancer may help find new biomarkers and therapeutic targets for ovarian cancer. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression, mostly at the posttranscriptional stage, through binding to mRNA targets and inducing translational repression or degradation of target via the RNA-induced silencing complex. Over the last two decades, the role of miRNAs in the pathogenesis of various human cancers, including ovarian cancer, has been documented in multiple studies. Consequently, these small RNAs could be considered as reliable markers for prognosis and early diagnosis. Furthermore, given the function of miRNAs in various cellular pathways, including cell survival and differentiation, targeting miRNAs could be an interesting approach for the treatment of human cancers. Here, we review our current understanding of the most updated role of the important dysregulation of miRNAs and their roles in the progression and metastasis of ovarian cancer. Furthermore, we meticulously discuss the significance of miRNAs as prognostic and diagnostic markers. Lastly, we mention the opportunities and the efforts made for targeting ovarian cancer through inhibition and/or stimulation of the miRNAs.

scholarly journals DICER Inactivation Identifies Pancreatic β-Cell “Disallowed” Genes Targeted by MicroRNAs

2015 ◽  
Vol 29 (7) ◽  
pp. 1067-1079 ◽  
Author(s):  
Aida Martinez-Sanchez ◽  
Marie-Sophie Nguyen-Tu ◽  
Guy A. Rutter
Keyword(s):  
Molecular Mechanisms ◽  
Early Stage ◽  
Cell Mass ◽  
Noncoding Rnas ◽  
Sole Source ◽  
Rnase Iii ◽  
Β Cells ◽  
Β Cell ◽  
Small Noncoding Rnas ◽  
And Function

Abstract Pancreatic β-cells are the body's sole source of circulating insulin and essential for the maintenance of blood glucose homeostasis. Levels of up to 66 “disallowed” genes, which are strongly expressed and play housekeeping roles in most other mammalian tissues, are unusually low in β-cells. The molecular mechanisms involved in repressing these genes are largely unknown. Here, we explore the role in gene disallowance of microRNAs (miRNAs), a type of small noncoding RNAs that silence gene expression at the posttranscriptional level and are essential for β-cell development and function. To selectively deplete miRNAs from adult β-cells, the miRNA-processing enzyme DICER was inactivated by deletion of the RNase III domain with a tamoxifen-inducible Pdx1CreER transgene. In this model, β-cell dysfunction was apparent 2 weeks after recombination and preceded a decrease in insulin content and loss of β-cell mass. Of the 14 disallowed genes studied, quantitative RT-quantitative real-time PCR revealed that 6 genes (Fcgrt, Igfbp4, Maf, Oat, Pdgfra, and Slc16a1) were up-regulated (1.4- to 2.1-fold, P < .05) at this early stage. Expression of luciferase constructs bearing the 3′-untranslated regions of the corresponding mRNAs in wild-type or DICER-null β-cells demonstrated that Fcgrt, Oat, and Pdgfra are miRNA direct targets. We thus reveal a role for miRNAs in the regulation of disallowed genes in β-cells and provide evidence for a novel means through which noncoding RNAs control the functional identity of these cells independently of actions on β-cell mass.

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