scholarly journals RNA Modifications and RNA Metabolism in Neurological Disease Pathogenesis

2021 ◽  
Vol 22 (21) ◽  
pp. 11870
Author(s):  
Biswanath Chatterjee ◽  
Che-Kun James Shen ◽  
Pritha Majumder
Keyword(s):  
Gene Expression ◽  
Stress Responses ◽  
Neurological Diseases ◽  
Rna Metabolism ◽  
Cellular Heterogeneity ◽  
Rna Modifications ◽  
Sequencing Technologies ◽  
Physiological Processes ◽  
Non Coding Rna ◽  
The Stability

The intrinsic cellular heterogeneity and molecular complexity of the mammalian nervous system relies substantially on the dynamic nature and spatiotemporal patterning of gene expression. These features of gene expression are achieved in part through mechanisms involving various epigenetic processes such as DNA methylation, post-translational histone modifications, and non-coding RNA activity, amongst others. In concert, another regulatory layer by which RNA bases and sugar residues are chemically modified enhances neuronal transcriptome complexity. Similar RNA modifications in other systems collectively constitute the cellular epitranscriptome that integrates and impacts various physiological processes. The epitranscriptome is dynamic and is reshaped constantly to regulate vital processes such as development, differentiation and stress responses. Perturbations of the epitranscriptome can lead to various pathogenic conditions, including cancer, cardiovascular abnormalities and neurological diseases. Recent advances in next-generation sequencing technologies have enabled us to identify and locate modified bases/sugars on different RNA species. These RNA modifications modulate the stability, transport and, most importantly, translation of RNA. In this review, we discuss the formation and functions of some frequently observed RNA modifications—including methylations of adenine and cytosine bases, and isomerization of uridine to pseudouridine—at various layers of RNA metabolism, together with their contributions to abnormal physiological conditions that can lead to various neurodevelopmental and neurological disorders.

scholarly journals Emerging Roles of Non-Coding RNA in Neuronal Function and Dysfunction

2021 ◽  
Author(s):  
Steven G. Fagan ◽  
Shona Pfeiffer
Keyword(s):  
Gene Expression ◽  
Stress Responses ◽  
Neurological Diseases ◽  
Regulation Of Gene Expression ◽  
Protein Translation ◽  
Sequencing Technologies ◽  
Non Coding Rna ◽  
Cellular Stress Responses ◽  
Novel Biomarkers ◽  
Underlying Pathophysiology

Advancements in RNA sequencing technologies in recent years have contributed greatly to our understanding of the transcriptome and the now widely recognized multifaceted functions of RNA. The discovery and functional analysis of an increasing number of novel small non-coding RNAs (ncRNAs) has highlighted their importance as critical regulators of gene expression and brain function. In particular, two diverse classes of ncRNAs, microRNAs (miRNAs) and tRNA-derived small RNAs (tsRNAs), are especially abundant in the nervous system and play roles in regulation of gene expression and protein translation, cellular stress responses and complex underlying pathophysiology of neurological diseases. This chapter will discuss the most recent findings highlighting the dysregulation, functions and regulatory roles of ncRNAs in the pathophysiological mechanisms of neurological disorders and their relevance as novel biomarkers of injury and therapeutic agents.

scholarly journals Current Practices for Reference Gene Selection in RT-qPCR of Aspergillus: Outlook and Recommendations for the Future

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 960
Author(s):  
Meagan Archer ◽  
Jianping Xu
Keyword(s):  
Gene Expression ◽  
Reference Gene ◽  
Reference Genes ◽  
Gene Selection ◽  
Quantitative Polymerase Chain Reaction ◽  
Specific Method ◽  
Experimental Conditions ◽  
Reference Gene Selection ◽  
Physiological Processes ◽  
The Stability

Aspergillus is a genus of filamentous fungi with vast geographic and ecological distributions. Species within this genus are clinically, agriculturally and biotechnologically relevant, leading to increasing interest in elucidating gene expression dynamics of key metabolic and physiological processes. Reverse-transcription quantitative Polymerase Chain Reaction (RT-qPCR) is a sensitive and specific method of quantifying gene expression. A crucial step for comparing RT-qPCR results between strains and experimental conditions is normalisation to experimentally validated reference gene(s). In this review, we provide a critical analysis of current reference gene selection and validation practices for RT-qPCR gene expression analyses of Aspergillus. Of 90 primary research articles obtained through our PubMed query, 17 experimentally validated the reference gene(s) used. Twenty reference genes were used across the 90 studies, with beta-tubulin being the most used reference gene, followed by actin, 18S rRNA and glyceraldehyde 3-phosphate dehydrogenase. Sixteen of the 90 studies used multiple reference genes for normalisation. Failing to experimentally validate the stability of reference genes can lead to conflicting results, as was the case for four studies. Overall, our review highlights the need to experimentally validate reference genes in RT-qPCR studies of Aspergillus.

Gene expression profile of aging in human muscle

2003 ◽  
Vol 14 (2) ◽  
pp. 149-159 ◽  
Author(s):  
Stephen Welle ◽  
Andrew I. Brooks ◽  
Joseph M. Delehanty ◽  
Nancy Needler ◽  
Charles A. Thornton
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Stress Responses ◽  
Rna Binding ◽  
Splice Variants ◽  
Expression Profiles ◽  
Vastus Lateralis ◽  
Mitochondrial Protein ◽  
Cellular Heterogeneity ◽  
Growth Factor Signaling

Studies of gene expression related to aging of skeletal muscle have included few subjects or a limited number of genes. We conducted the present study to produce more comprehensive gene expression profiles. RNA was extracted from vastus lateralis biopsies obtained from healthy young (21–27 yr old, n = 8) and older men (67–75 yr old, n = 8) and was analyzed with high-density oligonucleotide arrays. Of the ∼44,000 probe sets on the arrays, ∼18,000 yielded adequate signals for statistical analysis. There were ∼700 probe sets for which t-tests or rank sum tests indicated a difference ( P ≤ 0.01) in mean expression between young and old and for which the estimated false discovery rate was <10%. Most of these differences were less than 1.5-fold in magnitude. Genes that encode proteins involved in energy metabolism and mitochondrial protein synthesis were expressed at a lower level in older muscle. Genes encoding metallothioneins, high-mobility-group proteins, heterogeneous nuclear ribonucleoproteins and other RNA binding/processing proteins, and components of the ubiquitin-proteasome proteolytic pathway were expressed at higher levels in older muscle. Expression of numerous genes involved with stress responses, hormone/cytokine/growth factor signaling, control of the cell cycle and apoptosis, and transcriptional regulation appeared to be affected by aging. More transcripts were detected in older muscle, suggesting dedifferentiation, an increased number of splice variants, or increased cellular heterogeneity. We conclude that in human skeletal muscle the expression of many genes tends to increase or decrease between the third and seventh decades. The changes are modest when averaged over all of the cells in the tissue.

scholarly journals The role of m6A, m5C and Ψ RNA modifications in cancer: Novel therapeutic opportunities

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Paz Nombela ◽  
Borja Miguel-López ◽  
Sandra Blanco
Keyword(s):  
Gene Expression ◽  
Rna Processing ◽  
Therapeutic Potential ◽  
Biological Processes ◽  
Rna Modifications ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
And Function ◽  
Made In

AbstractRNA modifications have recently emerged as critical posttranscriptional regulators of gene expression programmes. Significant advances have been made in understanding the functional role of RNA modifications in regulating coding and non-coding RNA processing and function, which in turn thoroughly shape distinct gene expression programmes. They affect diverse biological processes, and the correct deposition of many of these modifications is required for normal development. Alterations of their deposition are implicated in several diseases, including cancer. In this Review, we focus on the occurrence of N6-methyladenosine (m6A), 5-methylcytosine (m5C) and pseudouridine (Ψ) in coding and non-coding RNAs and describe their physiopathological role in cancer. We will highlight the latest insights into the mechanisms of how these posttranscriptional modifications influence tumour development, maintenance, and progression. Finally, we will summarize the latest advances on the development of small molecule inhibitors that target specific writers or erasers to rewind the epitranscriptome of a cancer cell and their therapeutic potential.

scholarly journals MicroRNAs: From Junk RNA to Life Regulators and Their Role in Cardiovascular Disease

2021 ◽  
Vol 11 (4) ◽  
pp. 230-254
Author(s):  
Federica Amodio ◽  
Martina Caiazza ◽  
Fabio Fimiani ◽  
Paolo Calabrò ◽  
Giuseppe Limongelli
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Cell Communication ◽  
Transcriptional Level ◽  
Negative Regulators ◽  
Cellular Processes ◽  
Non Coding Rna ◽  
New Perspective ◽  
Therapeutic Tools ◽  
The Stability

MicroRNAs (miRNAs) are single-stranded small non-coding RNA (18–25 nucleotides) that until a few years ago were considered junk RNA. In the last twenty years, they have acquired more importance thanks to the understanding of their influence on gene expression and their role as negative regulators at post-transcriptional level, influencing the stability of messenger RNA (mRNA). Approximately 5% of the genome encodes miRNAs which are responsible for regulating numerous signaling pathways, cellular processes and cell-to-cell communication. In the cardiovascular system, miRNAs control the functions of various cells, such as cardiomyocytes, endothelial cells, smooth muscle cells and fibroblasts, playing a role in physiological and pathological processes and seeming also related to variations in contractility and hereditary cardiomyopathies. They provide a new perspective on the pathophysiology of disorders such as hypertrophy, fibrosis, arrhythmia, inflammation and atherosclerosis. MiRNAs are differentially expressed in diseased tissue and can be released into the circulation and then detected. MiRNAs have become interesting for the development of new diagnostic and therapeutic tools for various diseases, including heart disease. In this review, the concept of miRNAs and their role in cardiomyopathies will be introduced, focusing on their potential as therapeutic and diagnostic targets (as biomarkers).

Ageing and sources of transcriptional heterogeneity

2019 ◽  
Vol 400 (7) ◽  
pp. 867-878 ◽  
Author(s):  
Chrysa Nikopoulou ◽  
Swati Parekh ◽  
Peter Tessarz
Keyword(s):  
Gene Expression ◽  
New Technologies ◽  
Biological Function ◽  
Recent Literature ◽  
Cellular Heterogeneity ◽  
Transcriptional Noise ◽  
Single Cell Sequencing ◽  
Sequencing Technologies ◽  
Recent Developments ◽  
Cell To Cell Variability

Abstract Cellular heterogeneity is an important contributor to biological function and is employed by cells, tissues and organisms to adapt, compensate, respond, defend and/or regulate specific processes. Research over the last decades has revealed that transcriptional noise is a major driver for cell-to-cell variability. In this review we will discuss sources of transcriptional variability, in particular bursting of gene expression and how it could contribute to cellular states and fate decisions. We will highlight recent developments in single cell sequencing technologies that make it possible to address cellular heterogeneity in unprecedented detail. Finally, we will review recent literature, in which these new technologies are harnessed to address pressing questions in the field of ageing research, such as transcriptional noise and cellular heterogeneity in the course of ageing.

scholarly journals Dynamic Signature of tRNA-Derived small RNAs in Cancer Pathogenesis as a Promising Valuable Approach

2020 ◽  
Author(s):  
Somayeh Vafaei ◽  
Fahimeh Fattahi ◽  
Maryam Sahlolbei ◽  
Zahra Madjd ◽  
Ayna Yazdanpanah ◽  
...  
Keyword(s):  
Gene Expression ◽  
Small Rnas ◽  
Gene Expression Regulation ◽  
Transfer Rnas ◽  
Physiological Processes ◽  
Cancer Pathogenesis ◽  
Non Coding Rna ◽  
Cancer Field ◽  
Cancer Types ◽  
Dynamic Signature

Abstract Background: Non-coding RNAs are a cluster of RNAs that do not encode functional proteins, and involve infrastructural and regulatory types, which transfer RNAs (tRNAs) belong to former and small RNAs (sRNA) to the latter one. Recently, tRNA-derived small RNAs (tDRs) were discovered among small non-coding RNA, as the newly discovered regulatory small RNA. It plays a role in pathological and physiological processes, which is frequently dysregulated in gene expression regulation. tsRNAs can be bounded to argonaute proteins and piwi proteins such as miRNAs and piRNAs sequentially. In addition, it can interact with DNA and histone methylation machinery Results: In initial searching, 2744 unique articles were identified by bio electronically search of following databases: PubMed, Embase, Web of Science, Scopus, and google scholar up to 25 February 2020. Finally, after Full-text assessment 48 related article to gene expression profiling tsRNA in cancer were achieved. Conclusions: In this systematic review, we summarized the most recent findings related to the expression of tsRNAs in 17 cancer types. We suggested that tsRNA in cancer field attracted the researchers' focus and effectively facilitated diagnostic and therapy approaches.

scholarly journals Arabidopsis heat shock transcription factor HSFA7b positively mediates salt stress tolerance by binding to an E-box-like motif to regulate gene expression

2019 ◽  
Vol 70 (19) ◽  
pp. 5355-5374 ◽  
Author(s):  
Dandan Zang ◽  
Jingxin Wang ◽  
Xin Zhang ◽  
Zhujun Liu ◽  
Yucheng Wang
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Heat Shock ◽  
Salt Tolerance ◽  
Stress Responses ◽  
Ion Homeostasis ◽  
Cellulose Synthase ◽  
Regulate Gene Expression ◽  
E Box ◽  
Regulate Gene

Abstract Plant heat shock transcription factors (HSFs) are involved in heat and other abiotic stress responses. However, their functions in salt tolerance are little known. In this study, we characterized the function of a HSF from Arabidopsis, AtHSFA7b, in salt tolerance. AtHSFA7b is a nuclear protein with transactivation activity. ChIP-seq combined with an RNA-seq assay indicated that AtHSFA7b preferentially binds to a novel cis-acting element, termed the E-box-like motif, to regulate gene expression; it also binds to the heat shock element motif. Under salt conditions, AtHSFA7b regulates its target genes to mediate serial physiological changes, including maintaining cellular ion homeostasis, reducing water loss rate, decreasing reactive oxygen species accumulation, and adjusting osmotic potential, which ultimately leads to improved salt tolerance. Additionally, most cellulose synthase-like (CSL) and cellulose synthase (CESA) family genes were inhibited by AtHSFA7b; some of them were randomly selected for salt tolerance characterization, and they were mainly found to negatively modulate salt tolerance. By contrast, some transcription factors (TFs) were induced by AtHSFA7b; among them, we randomly identified six TFs that positively regulate salt tolerance. Thus, AtHSFA7b serves as a transactivator that positively mediates salinity tolerance mainly through binding to the E-box-like motif to regulate gene expression.

Sign in / Sign up

Export Citation Format

Share Document