scholarly journals Emerging Roles of N6-Methyladenosine Modification in Neurodevelopment and Neurodegeneration

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2694
Author(s):  
Liqi Shu ◽  
Xiaoli Huang ◽  
Xuejun Cheng ◽  
Xuekun Li
Keyword(s):  
Gene Expression ◽  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Neuronal Development ◽  
Current Knowledge ◽  
Biological Processes ◽  
Messenger Rnas ◽  
Domain Family ◽  
Yth Domain ◽  
Essential Function

N6-methyladenosine (m6A), the most abundant modification in messenger RNAs (mRNAs), is deposited by methyltransferases (“writers”) Mettl3 and Mettl14 and erased by demethylases (“erasers”) Fto and Alkbh5. m6A can be recognized by m6A-binding proteins (“readers”), such as Yth domain family proteins (Ythdfs) and Yth domain-containing protein 1 (Ythdc1). Previous studies have indicated that m6A plays an essential function in various fundamental biological processes, including neurogenesis and neuronal development. Dysregulated m6A modification contributes to neurological disorders, including neurodegenerative diseases. In this review, we summarize the current knowledge about the roles of m6A machinery, including writers, erasers, and readers, in regulating gene expression and the function of m6A in neurodevelopment and neurodegeneration. We also discuss the perspectives for studying m6A methylation.

scholarly journals The Study of Cerebrospinal Fluid microRNAs in Spinal Cord Injury and Neurodegenerative Diseases: Methodological Problems and Possible Solutions

2021 ◽  
Vol 23 (1) ◽  
pp. 114
Author(s):  
Irina Baichurina ◽  
Victor Valiullin ◽  
Victoria James ◽  
Albert Rizvanov ◽  
Yana Mukhamedshina
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cerebrospinal Fluid ◽  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Rna Isolation ◽  
Cord Injury

Despite extensive research on neurological disorders, unanswered questions remain regarding the molecular mechanisms underpinning the course of these diseases, and the search continues for effective biomarkers for early diagnosis, prognosis, or therapeutic intervention. These questions are especially acute in the study of spinal cord injury (SCI) and neurodegenerative diseases. It is believed that the changes in gene expression associated with processes triggered by neurological disorders are the result of post-transcriptional gene regulation. microRNAs (miRNAs) are key regulators of post-transcriptional gene expression and, as such, are often looked to in the search for effective biomarkers. We propose that cerebrospinal fluid (CSF) is potentially a source of biomarkers since it is in direct contact with the central nervous system and therefore may contain biomarkers indicating neurodegeneration or damage to the brain and spinal cord. However, since the abundance of miRNAs in CSF is low, their isolation and detection is technically difficult. In this review, we evaluate the findings of recent studies of CSF miRNAs as biomarkers of spinal cord injury (SCI) and neurodegenerative diseases. We also summarize the current knowledge concerning the methods of studying miRNA in CSF, including RNA isolation and normalization of the data, highlighting the caveats of these approaches and possible solutions.

scholarly journals Nuclear Functions of TOR: Impact on Transcription and the Epigenome

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 641 ◽  
Author(s):  
R. Nicholas Laribee ◽  
Ronit Weisman
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Protein Kinase ◽  
Neurological Disorders ◽  
Regulation Of Gene Expression ◽  
Clinical Implications ◽  
Biological Processes ◽  
The Core ◽  
Regulation Of Metabolism ◽  
Pharmacological Target

The target of rapamycin (TOR) protein kinase is at the core of growth factor- and nutrient-dependent signaling pathways that are well-known for their regulation of metabolism, growth, and proliferation. However, TOR is also involved in the regulation of gene expression, genomic and epigenomic stability. TOR affects nuclear functions indirectly through its activity in the cytoplasm, but also directly through active nuclear TOR pools. The mechanisms by which TOR regulates its nuclear functions are less well-understood compared with its cytoplasmic activities. TOR is an important pharmacological target for several diseases, including cancer, metabolic and neurological disorders. Thus, studies of the nuclear functions of TOR are important for our understanding of basic biological processes, as well as for clinical implications.

scholarly journals A Census and Categorization Method of Epitranscriptomic Marks

2020 ◽  
Vol 21 (13) ◽  
pp. 4684
Author(s):  
Julia Mathlin ◽  
Loredana Le Pera ◽  
Teresa Colombo
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Messenger Rnas ◽  
Rna Modifications ◽  
Chemical Modifications ◽  
Rna Molecules ◽  
Transcriptional Regulatory ◽  
Functional Relevance

In the past few years, thorough investigation of chemical modifications operated in the cells on ribonucleic acid (RNA) molecules is gaining momentum. This new field of research has been dubbed “epitranscriptomics”, in analogy to best-known epigenomics, to stress the potential of ensembles of RNA modifications to constitute a post-transcriptional regulatory layer of gene expression orchestrated by writer, reader, and eraser RNA-binding proteins (RBPs). In fact, epitranscriptomics aims at identifying and characterizing all functionally relevant changes involving both non-substitutional chemical modifications and editing events made to the transcriptome. Indeed, several types of RNA modifications that impact gene expression have been reported so far in different species of cellular RNAs, including ribosomal RNAs, transfer RNAs, small nuclear RNAs, messenger RNAs, and long non-coding RNAs. Supporting functional relevance of this largely unknown regulatory mechanism, several human diseases have been associated directly to RNA modifications or to RBPs that may play as effectors of epitranscriptomic marks. However, an exhaustive epitranscriptome’s characterization, aimed to systematically classify all RNA modifications and clarify rules, actors, and outcomes of this promising regulatory code, is currently not available, mainly hampered by lack of suitable detecting technologies. This is an unfortunate limitation that, thanks to an unprecedented pace of technological advancements especially in the sequencing technology field, is likely to be overcome soon. Here, we review the current knowledge on epitranscriptomic marks and propose a categorization method based on the reference ribonucleotide and its rounds of modifications (“stages”) until reaching the given modified form. We believe that this classification scheme can be useful to coherently organize the expanding number of discovered RNA modifications.

scholarly journals Systematic Analyses of the Role of the Reader Protein of N6-Methyladenosine RNA Methylation, YTH Domain Family 2, in Liver Hepatocellular Carcinoma

2020 ◽  
Vol 7 ◽  
Author(s):  
Xiang-yang Shao ◽  
Jin Dong ◽  
Han Zhang ◽  
Ying-song Wu ◽  
Lei Zheng
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Immune Cells ◽  
Cancer Genome ◽  
Gene Set Enrichment Analysis ◽  
Domain Family ◽  
Rna Methylation ◽  
Yth Domain ◽  
Liver Hepatocellular Carcinoma

BackgroundYTH domain family (YTHDF) 2 acts as a “reader” protein for RNA methylation, which is important in tumor regulation. However, the effect of YTHDF2 in liver hepatocellular carcinoma (LIHC) has yet to be elucidated.MethodsWe explored the role of YTHDF2 in LIHC based on publicly available datasets [The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO)]. A bioinformatics approach was employed to analyze YTHDF2. Logistic regression analyses were applied to analyze the correlation between YTHDF2 expression and clinical characteristics. To evaluate the effect of YTHDF2 on the prognosis of LIHC patients, we used Kaplan–Meier (K–M) curves. Gene set enrichment analysis (GSEA) was undertaken using TCGA dataset. Univariate and multivariate Cox analyses were used to ascertain the correlations between YTHDF2 expression and clinicopathologic characteristics with survival. Genes co-expressed with YTHDF2 were identified and detected using publicly available datasets [LinkedOmics, University of California, Santa Cruz (UCSC), Gene Expression Profiling Interactive Analysis (GEPIA), and GEO]. Correlations between YTHDF2 and infiltration of immune cells were investigated by Tumor Immune Estimation Resource (TIMER) and GEPIA.ResultsmRNA and protein expression of YTHDF2 was significantly higher in LIHC tissues than in non-cancerous tissues. High YTHDF2 expression in LIHC was associated with poor prognostic clinical factors (high stage, grade, and T classification). K–M analyses indicated that high YTHDF2 expression was correlated with an unfavorable prognosis. Univariate and multivariate Cox analyses revealed that YTHDF2 was an independent factor for a poor prognosis in LIHC patients. GSEA revealed that the high-expression phenotype of YTHDF2 was consistent with the molecular pathways implicated in LIHC carcinogenesis. Analyses of receiver operating characteristic curves showed that YTHDF2 might have a diagnostic value in LIHC patients. YTHDF2 expression was associated positively with SF3A3 expression, which implied that they may cooperate in LIHC progression. YTHDF2 expression was associated with infiltration of immune cells and their marker genes. YTHDF2 had the potential to regulate polarization of tumor-associated macrophages, induce T-cell exhaustion, and activate T-regulatory cells.ConclusionYTHDF2 may be a promising biomarker for the diagnosis and prognosis of LIHC and may provide new directions and strategies for LIHC treatment.

scholarly journals Long Non-coding RNAs in Pathogenesis of Neurodegenerative Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Shiyue Zhou ◽  
Xiao Yu ◽  
Min Wang ◽  
Yujie Meng ◽  
Dandan Song ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Chromatin Remodeling ◽  
Mrna Stability ◽  
Neurological Disorders ◽  
Regulation Of Gene Expression ◽  
Tau Phosphorylation ◽  
Research Progress ◽  
Biological Processes ◽  
Non Coding Rnas ◽  
Lateral Sclerosis

Emerging evidence addresses the link between the aberrant epigenetic regulation of gene expression and numerous diseases including neurological disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). LncRNAs, a class of ncRNAs, have length of 200 nt or more, some of which crucially regulate a variety of biological processes such as epigenetic-mediated chromatin remodeling, mRNA stability, X-chromosome inactivation and imprinting. Aberrant regulation of the lncRNAs contributes to pathogenesis of many diseases, such as the neurological disorders at the transcriptional and post-transcriptional levels. In this review, we highlight the latest research progress on the contributions of some lncRNAs to the pathogenesis of neurodegenerative diseases via varied mechanisms, such as autophagy regulation, Aβ deposition, neuroinflammation, Tau phosphorylation and α-synuclein aggregation. Meanwhile, we also address the potential challenges on the lncRNAs-mediated epigenetic study to further understand the molecular mechanism of the neurodegenerative diseases.

scholarly journals Effects of Dietary Fatty Acids on Gene Expression and Biological Processes in Different Tissues of Pigs: A Review

2021 ◽  
Author(s):  
Simara Larissa Fanalli ◽  
Bruna Pereira Martins da Silva ◽  
Bruna Petry ◽  
Miguel Henrique de Almeida Santana ◽  
Guilherme Henrique Gebim Polizel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Production Systems ◽  
Current Knowledge ◽  
Dietary Fatty Acids ◽  
Regulation Of Transcription ◽  
Biological Processes ◽  
Finishing Pigs ◽  
Production Traits ◽  
Different Tissues

Studies on the influence of dietary components and their effects are fundamental for nutrigenomics, or the study of how nutrients can be cellular sensors, how they affect biological processes and gene expression in different tissues. Lipids are an important source of fatty acids (FA) and energy and are fundamental to biological processes and influence the regulation of transcription. Pigs are excellent model to study nutrigenomics, particularly lipid metabolism because the deposition and composition of FA in their tissues reflect the composition of FA in their diet. Recent studies show that FA supplementation is important in production systems, such as growing and finishing pigs, as it can improve the energy value of the feed, help reduce costs, improve animal welfare, and influence the nutritional value of the meat. Studies show that oleic (OA), linoleic (LA), docosahexaenoic (DHA), and eicosapentaenoic (EPA) acids are associated with the regulation of transcription in tissues such as muscle, liver, adipose tissue, and brain. Other studies indicate that EPA and DHA are associated with changes in specific signaling pathways, altering gene expression and biophysical properties of membranes. This review, therefore, focuses on the current knowledge of the effects of dietary FA on production traits and gene expression.

scholarly journals Specific Roles of MicroRNAs in Their Interactions with Environmental Factors

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Juan Wang ◽  
Qinghua Cui
Keyword(s):  
Gene Expression ◽  
Cell Growth ◽  
Environmental Factors ◽  
Cigarette Smoking ◽  
Current Knowledge ◽  
Wide Spectrum ◽  
Exercise Stress ◽  
Biological Processes ◽  
Industrial Materials ◽  
Posttranscriptional Level

MicroRNAs (miRNAs) have emerged as critical regulators of gene expression by modulating numerous target mRNAs expression at posttranscriptional level. Extensive studies have shown that miRNAs are critical in various important biological processes, including cell growth, proliferation, differentiation, development, and apoptosis. In terms of their importance, miRNA dysfunction has been associated with a broad range of diseases. Increased number of studies have shown that miRNAs can functionally interact with a wide spectrum of environmental factors (EFs) including drugs, industrial materials, virus and bacterial pathogens, cigarette smoking, alcohol, nutrition, sleep, exercise, stress, and radiation. More importantly, the interactions between miRNAs and EFs have been shown to play critical roles in determining abnormal phenotypes and diseases. In this paper, we propose an outline of the current knowledge about specific roles of miRNAs in their interactions with various EFs and analyze the literatures detailing miRNAs-EFs interactions in the context of various of diseases.

scholarly journals YTH Domain Proteins: A Family of m6A Readers in Cancer Progression

2021 ◽  
Vol 11 ◽  
Author(s):  
Yirong Xu ◽  
Wei Zhang ◽  
Feng Shen ◽  
Xi Yang ◽  
Huilan Liu ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Rna Degradation ◽  
Translation Regulation ◽  
Future Research ◽  
Messenger Rnas ◽  
Domain Family ◽  
Research Directions ◽  
New Ideas ◽  
Future Research Directions ◽  
Yth Domain

N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNAs (mRNAs). m6A RNA methylation is involved in all stages of RNA life cycle, from RNA processing, nuclear output, translation regulation to RNA degradation, indicating that m6A has various functions affecting RNA metabolism positively or negatively. Reading proteins are vital in regulating the translation and stability of m6A mRNAs positively or negatively. Recent studies have enhanced the understanding of the molecular mechanism of the YT521-B homology (YTH) domain family and the modification of m6A. This study aimed to review the specific mechanisms, functions, and interactions of the YTH domain protein family. It also discussed future research directions, thus providing new ideas for the clinical diagnosis and targeted therapy of cancer.

scholarly journals Proteome Linked Biochemical Targets: Can Repair Defective Cellular Physiological Mechanisms?

2021 ◽  
Vol 55 (S2) ◽  
pp. 49-70
Keyword(s):  
Neurodegenerative Diseases ◽  
Natural Compound ◽  
Neuronal Development ◽  
Current Knowledge ◽  
Cost Effective ◽  
Protein Aggregates ◽  
Natural Compounds ◽  
Therapeutic Interventions ◽  
Neuronal Homeostasis ◽  
Neuronal Processes

Major cause of proteopathies is the accumulation of unwanted mutant and aberrant proteins. We know that imperfect ageing is one of chief risk factor for most neurodegenerative diseases. Neurodegenerative diseases are characterized by mutant misfolded protein aggregates developing neural stress and debilitating several neuronal processes. Reducing the levels of these abnormal proteins using various natural compounds can be a promising possible therapeutic strategy. But the advancement of natural compound-based therapies in neurodegeneration and imperfect ageing treatment has been impeded by different challenges and unknown molecular patho-mechansim. The complexity in the causative factors generating protein aggregates in neurons and their respective path towards cell death is high, making it a difficult to treat disorder. Several plant based compounds have proven to promote different neuronal homeostasis mechanisms. However, there is a pressing necessity to screen, find and develop cost-effective natural compound-based new therapeutic interventions which can be useful for clinical purposes in treating neurodegenerative ailments. It is critical to discuss and elaborate the applications of few important natural compounds and their connections with following mechanisms: protein disposal machineries, apoptosis, neuroinflammation, neuronal development, synaptogenesis and neural homeostasis. This article summarizes the current knowledge and discusses the unanswered questions linked with the natural compounds and their promising therapeutic avenues primarily focusing on neurodegenerative diseases and defective neurobiological mechanisms.

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