scholarly journals MicroRNA biogenesis: Epigenetic modifications as another layer of complexity to the microRNA expression regulation

2017 ◽  
Vol 63 (4) ◽  
Author(s):  
Susheel Sagar Bhat ◽  
Artur Jarmolowski ◽  
Zofia Szweykowska-Kulinska
Keyword(s):  
Epigenetic Modifications ◽  
Expression Regulation ◽  
Microrna Expression ◽  
Regulatory Mechanisms ◽  
Mirna Biogenesis ◽  
Biological Processes ◽  
Critical Importance ◽  
Microrna Biogenesis ◽  
Regulatory Machinery

Since their discovery, microRNAs have led to a huge shift in our understanding of the regulation of key biological processes. The discovery of epigenetic modifications that affect microRNA expression has added another layer of complexity to the already tightly controlled regulatory machinery. The presence of N6-methyl-adenosine (m6A) mark and its critical importance in miRNA biogenesis in animals adds to our understanding of the regulatory mechanisms.

scholarly journals Protein lysine crotonylation: past, present, perspective

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Gaoyue Jiang ◽  
Chunxia Li ◽  
Meng Lu ◽  
Kefeng Lu ◽  
Huihui Li
Keyword(s):  
Cross Talk ◽  
Tissue Injury ◽  
Regulatory Mechanisms ◽  
Biological Processes ◽  
Histone Proteins ◽  
Physiological Functions ◽  
Neuropsychiatric Disease ◽  
Enzymatic Mechanisms ◽  
Substrate Proteins ◽  
Tools And Methods

AbstractLysine crotonylation has been discovered in histone and non-histone proteins and found to be involved in diverse diseases and biological processes, such as neuropsychiatric disease, carcinogenesis, spermatogenesis, tissue injury, and inflammation. The unique carbon–carbon π-bond structure indicates that lysine crotonylation may use distinct regulatory mechanisms from the widely studied other types of lysine acylation. In this review, we discussed the regulation of lysine crotonylation by enzymatic and non-enzymatic mechanisms, the recognition of substrate proteins, the physiological functions of lysine crotonylation and its cross-talk with other types of modification. The tools and methods for prediction and detection of lysine crotonylation were also described.

scholarly journals Emerging multifaceted roles of BAP1 complexes in biological processes

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Aileen Patricia Szczepanski ◽  
Lu Wang
Keyword(s):  
Transcriptional Repression ◽  
Target Genes ◽  
Regulatory Mechanisms ◽  
Biological Processes ◽  
Multiprotein Complex ◽  
Downstream Target ◽  
Evolutionarily Conserved ◽  
Complex Forms ◽  
Polycomb Repressive Complex 1

AbstractHistone H2AK119 mono-ubiquitination (H2AK119Ub) is a relatively abundant histone modification, mainly catalyzed by the Polycomb Repressive Complex 1 (PRC1) to regulate Polycomb-mediated transcriptional repression of downstream target genes. Consequently, H2AK119Ub can also be dynamically reversed by the BAP1 complex, an evolutionarily conserved multiprotein complex that functions as a general transcriptional activator. In previous studies, it has been reported that the BAP1 complex consists of important biological roles in development, metabolism, and cancer. However, identifying the BAP1 complex’s regulatory mechanisms remains to be elucidated due to its various complex forms and its ability to target non-histone substrates. In this review, we will summarize recent findings that have contributed to the diverse functional role of the BAP1 complex and further discuss the potential in targeting BAP1 for therapeutic use.

scholarly journals Regulation of Energy Substrate Metabolism in Endurance Exercise

2021 ◽  
Vol 18 (9) ◽  
pp. 4963
Author(s):  
Abdullah F. Alghannam ◽  
Mazen M. Ghaith ◽  
Maha H. Alhussain
Keyword(s):  
Fatty Acids ◽  
Exercise Intensity ◽  
Fat Metabolism ◽  
Glycogen Storage ◽  
Regulatory Mechanisms ◽  
Critical Importance ◽  
Energy Substrate ◽  
Substrate Metabolism ◽  
Atp Turnover ◽  
Energy Demands

The human body requires energy to function. Adenosine triphosphate (ATP) is the cellular currency for energy-requiring processes including mechanical work (i.e., exercise). ATP used by the cells is ultimately derived from the catabolism of energy substrate molecules—carbohydrates, fat, and protein. In prolonged moderate to high-intensity exercise, there is a delicate interplay between carbohydrate and fat metabolism, and this bioenergetic process is tightly regulated by numerous physiological, nutritional, and environmental factors such as exercise intensity and duration, body mass and feeding state. Carbohydrate metabolism is of critical importance during prolonged endurance-type exercise, reflecting the physiological need to regulate glucose homeostasis, assuring optimal glycogen storage, proper muscle fuelling, and delaying the onset of fatigue. Fat metabolism represents a sustainable source of energy to meet energy demands and preserve the ‘limited’ carbohydrate stores. Coordinated neural, hormonal and circulatory events occur during prolonged endurance-type exercise, facilitating the delivery of fatty acids from adipose tissue to the working muscle for oxidation. However, with increasing exercise intensity, fat oxidation declines and is unable to supply ATP at the rate of the exercise demand. Protein is considered a subsidiary source of energy supporting carbohydrates and fat metabolism, contributing to approximately 10% of total ATP turnover during prolonged endurance-type exercise. In this review we present an overview of substrate metabolism during prolonged endurance-type exercise and the regulatory mechanisms involved in ATP turnover to meet the energetic demands of exercise.

scholarly journals NF90 modulates processing of a subset of human pri-miRNAs

2020 ◽  
Vol 48 (12) ◽  
pp. 6874-6888
Author(s):  
Giuseppa Grasso ◽  
Takuma Higuchi ◽  
Victor Mac ◽  
Jérôme Barbier ◽  
Marion Helsmoortel ◽  
...  
Keyword(s):  
Rna Binding ◽  
Mirna Biogenesis ◽  
Biological Processes ◽  
Mobility Shift ◽  
Double Stranded Rna ◽  
Genome Wide ◽  
Mammalian Genes ◽  
Mobility Shift Assay ◽  
Host Genes ◽  
Stable Structures

Abstract MicroRNAs (miRNAs) are predicted to regulate the expression of >60% of mammalian genes and play fundamental roles in most biological processes. Deregulation of miRNA expression is a hallmark of most cancers and further investigation of mechanisms controlling miRNA biogenesis is needed. The double stranded RNA-binding protein, NF90 has been shown to act as a competitor of Microprocessor for a limited number of primary miRNAs (pri-miRNAs). Here, we show that NF90 has a more widespread effect on pri-miRNA biogenesis than previously thought. Genome-wide approaches revealed that NF90 is associated with the stem region of 38 pri-miRNAs, in a manner that is largely exclusive of Microprocessor. Following loss of NF90, 22 NF90-bound pri-miRNAs showed increased abundance of mature miRNA products. NF90-targeted pri-miRNAs are highly stable, having a lower free energy and fewer mismatches compared to all pri-miRNAs. Mutations leading to less stable structures reduced NF90 binding while increasing pri-miRNA stability led to acquisition of NF90 association, as determined by RNA electrophoretic mobility shift assay (EMSA). NF90-bound and downregulated pri-miRNAs are embedded in introns of host genes and expression of several host genes is concomitantly reduced. These data suggest that NF90 controls the processing of a subset of highly stable, intronic miRNAs.

The Sucrose Non-Fermenting 1-Related Protein Kinase 2 (SnRK2) Genes Are Multifaceted Players in Plant Growth, Development and Response to Environmental Stimuli

2019 ◽  
Vol 61 (2) ◽  
pp. 225-242 ◽  
Author(s):  
Xinguo Mao ◽  
Yuying Li ◽  
Shoaib Ur Rehman ◽  
Lili Miao ◽  
Yanfei Zhang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Specific Protein ◽  
Regulatory Mechanisms ◽  
Biological Processes ◽  
Related Protein ◽  
Biological Functions ◽  
Reversible Protein Phosphorylation ◽  
Growth Development ◽  
Regulatory Event

Abstract Reversible protein phosphorylation orchestrated by protein kinases and phosphatases is a major regulatory event in plants and animals. The SnRK2 subfamily consists of plant-specific protein kinases in the Ser/Thr protein kinase superfamily. Early observations indicated that SnRK2s are mainly involved in response to abiotic stress. Recent evidence shows that SnRK2s are multifarious players in a variety of biological processes. Here, we summarize the considerable knowledge of SnRK2s, including evolution, classification, biological functions and regulatory mechanisms at the epigenetic, post-transcriptional and post-translation levels.

scholarly journals Identification, Characterization, and Regulatory Mechanisms of a Novel EGR1 Splicing Isoform

2019 ◽  
Vol 20 (7) ◽  
pp. 1548 ◽  
Author(s):  
Vincenza Aliperti ◽  
Giulia Sgueglia ◽  
Francesco Aniello ◽  
Emilia Vitale ◽  
Laura Fucci ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cell Types ◽  
Regulatory Mechanisms ◽  
Brain Diseases ◽  
Regulation Of Transcription ◽  
Biological Processes ◽  
Activation Domain ◽  
Post Translational Modifications ◽  
Pathological Conditions ◽  
Proliferation And Apoptosis

EGR1 is a transcription factor expressed in many cell types that regulates genes involved in different biological processes including growth, proliferation, and apoptosis. Dysregulation of EGR1 expression has been associated with many pathological conditions such as tumors and brain diseases. Known molecular mechanisms underlying the control of EGR1 function include regulation of transcription, mRNA and protein stability, and post-translational modifications. Here we describe the identification of a splicing isoform for the human EGR1 gene. The newly identified splicing transcript encodes a shorter protein compared to the canonical EGR1. This isoform lacks a region belonging to the N-terminal activation domain and although it is capable of entering the nucleus, it is unable to activate transcription fully relative to the canonical isoform.

scholarly journals Epigenetic modifications of histones in cancer

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Zibo Zhao ◽  
Ali Shilatifard
Keyword(s):  
Histone Modifications ◽  
Functional Significance ◽  
Epigenetic Modifications ◽  
Cancer Development ◽  
Clinical Implications ◽  
Biological Processes ◽  
Disease Pathogenesis ◽  
Different Types ◽  
Histone Modifiers ◽  
The Many

AbstractThe epigenetic modifications of histones are versatile marks that are intimately connected to development and disease pathogenesis including human cancers. In this review, we will discuss the many different types of histone modifications and the biological processes with which they are involved. Specifically, we review the enzymatic machineries and modifications that are involved in cancer development and progression, and how to apply currently available small molecule inhibitors for histone modifiers as tool compounds to study the functional significance of histone modifications and their clinical implications.

A physiological perspective on targets of nitration in NO-based signaling networks in plants

2019 ◽  
Vol 70 (17) ◽  
pp. 4379-4389 ◽  
Author(s):  
Magdalena Arasimowicz-Jelonek ◽  
Jolanta Floryszak-Wieczorek
Keyword(s):  
Fatty Acids ◽  
Cellular Responses ◽  
Regulatory Mechanisms ◽  
Signaling Networks ◽  
Tyrosine Nitration ◽  
Biological Processes ◽  
Modeling Tools ◽  
Intracellular Traffic ◽  
Dna And Rna ◽  
Fine Tune

Abstract Although peroxynitrite (ONOO−) has been well documented as a nitrating cognate of nitric oxide (NO) in plant cells, modifications of proteins, fatty acids, and nucleotides by nitration are relatively under-explored topics in plant NO research. As a result, they are seen mainly as hallmarks of redox processes or as markers of nitro-oxidative stress under unfavorable conditions, similar to those observed in human and other animal systems. Protein tyrosine nitration is the best-known nitrative modification in the plant system and can be promoted by the action of both ONOO− and related NO-derived oxidants within the cell environment. Recent progress in ‘omics’ and modeling tools have provided novel biochemical insights into the physiological and pathophysiological fate of nitrated proteins. The nitration process can be specifically involved in various cell regulatory mechanisms that control redox signaling via nitrated cGMP or nitrated fatty acids. In addition, there is evidence to suggest that nitrative modifications of nucleotides embedded in DNA and RNA can be considered as smart switches of gene expression that fine-tune adaptive cellular responses to stress. This review highlights recent advances in our understanding of the potential implications of biotargets in the regulation of intracellular traffic and plant biological processes.

scholarly journals DNA methylation directs microRNA biogenesis in mammalian cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ohad Glaich ◽  
Shivang Parikh ◽  
Rachel E. Bell ◽  
Keren Mekahel ◽  
Maya Donyo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Mammalian Cells ◽  
Sequence Conservation ◽  
Mirna Biogenesis ◽  
Coding Sequence ◽  
Microrna Biogenesis ◽  
Flanking Regions

AbstractMicroRNA (miRNA) biogenesis initiates co-transcriptionally, but how the Microprocessor machinery pinpoints the locations of short precursor miRNA sequences within long flanking regions of the transcript is not known. Here we show that miRNA biogenesis depends on DNA methylation. When the regions flanking the miRNA coding sequence are highly methylated, the miRNAs are more highly expressed, have greater sequence conservation, and are more likely to drive cancer-related phenotypes than miRNAs encoded by unmethylated loci. We show that the removal of DNA methylation from miRNA loci leads to their downregulation. Further, we found that MeCP2 binding to methylated miRNA loci halts RNA polymerase II elongation, leading to enhanced processing of the primary miRNA by Drosha. Taken together, our data reveal that DNA methylation directly affects miRNA biogenesis.

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