Regulation of miRNA strand selection: follow the leader?

2014 ◽  
Vol 42 (4) ◽  
pp. 1135-1140 ◽  
Author(s):  
Hedda A. Meijer ◽  
Ewan M. Smith ◽  
Martin Bushell
Keyword(s):  
Rna Binding ◽  
Current Knowledge ◽  
Guide Strand ◽  
Disease States ◽  
Protein Activator ◽  
Passenger Strand ◽  
Key Characteristics ◽  
Dependent Protein ◽  
Activation Response ◽  
The Many

miRNA strand selection is the process that determines which of the two strands in a miRNA duplex becomes the active strand that is incorporated into the RISC (RNA-induced silencing complex) (named the guide strand, leading strand or miR) and which one gets degraded (the passenger strand or miR*). Thermodynamic features of the duplex appear to play an important role in this decision; the strand with the weakest binding at its 5′-end is more likely to become the guide strand. Other key characteristics of human miRNA guide strands are a U-bias at the 5′-end and an excess of purines, whereas the passenger strands have a C-bias at the 5′-end and an excess of pyrimidines. Several proteins are known to play a role in strand selection [Ago (Argonaute), DICER, TRBP (trans-activation response RNA-binding protein), PACT (protein activator of dsRNA-dependent protein kinase) and Xrn-1/2]; however, the mechanisms by which these proteins act are largely unknown. For several miRNAs the miR/miR* ratio varies dependent on cell type, developmental stage and in different disease states, suggesting that strand selection is a tightly controlled process. The present review discusses our current knowledge regarding the factors and processes involved in strand selection and the many questions that still remain.

Heracles and epilepsy: the sacred disease

2020 ◽  
Vol 78 (10) ◽  
pp. 660-662
Author(s):  
Eduardo ORREGO-GONZÁLEZ ◽  
Ana PERALTA-GARCÍA ◽  
Leonardo PALACIOS-SÁNCHEZ
Keyword(s):  
Current Knowledge ◽  
Greek Mythology ◽  
Corpus Hippocraticum ◽  
Ancient Times ◽  
The Many

ABSTRACT Epilepsy is one of the most dreaded and terrifying human afflictions. One of the many names it has received was Sacred Disease, during Greek times. Heracles served as a source of the divine connotation that epilepsy received in ancient times, as he was one of the most important demigods in Greek mythology. However, several authors have attributed Heracles’ actions to a seizure, including Hippocrates, who described the sacred disease on his “Corpus Hippocraticum.” This paper reviewed some of the publications on the myth and content of the text of Hippocrates, in relation to the current knowledge of the disease.

scholarly journals Unique Aspects of the Developing Lung Circulation: Structural Development and Regulation of Vasomotor Tone

2016 ◽  
Vol 6 (4) ◽  
pp. 407-425 ◽  
Author(s):  
Yuangsheng Gao ◽  
David N. Cornfield ◽  
Kurt R. Stenmark ◽  
Bernard Thébaud ◽  
Steven H. Abman ◽  
...  
Keyword(s):  
Lung Development ◽  
Lung Diseases ◽  
Vascular Tone ◽  
Current Knowledge ◽  
Normal Lung ◽  
Pulmonary Vasculature ◽  
Structural Development ◽  
Vasomotor Tone ◽  
Disease States ◽  
Vasculogenesis And Angiogenesis

This review summarizes our current knowledge on lung vasculogenesis and angiogenesis during normal lung development and the regulation of fetal and postnatal pulmonary vascular tone. In comparison to that of the adult, the pulmonary circulation of the fetus and newborn displays many unique characteristics. Moreover, altered development of pulmonary vasculature plays a more prominent role in compromised pulmonary vasoreactivity than in the adult. Clinically, a better understanding of the developmental changes in pulmonary vasculature and vasomotor tone and the mechanisms that are disrupted in disease states can lead to the development of new therapies for lung diseases characterized by impaired alveolar structure and pulmonary hypertension.

scholarly journals A Crosstalk between Diet, Microbiome and microRNA in Epigenetic Regulation of Colorectal Cancer

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2428
Author(s):  
Małgorzata Guz ◽  
Witold Jeleniewicz ◽  
Anna Malm ◽  
Izabela Korona-Glowniak
Keyword(s):  
Colorectal Cancer ◽  
Gastrointestinal Tract ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Current Knowledge ◽  
Vital Role ◽  
Disease States ◽  
Health And Disease ◽  
Dietary Components ◽  
Non Coding Rnas

A still growing interest between human nutrition in relation to health and disease states can be observed. Dietary components shape the composition of microbiota colonizing our gastrointestinal tract which play a vital role in maintaining human health. There is a strong evidence that diet, gut microbiota and their metabolites significantly influence our epigenome, particularly through the modulation of microRNAs. These group of small non-coding RNAs maintain cellular homeostasis, however any changes leading to impaired expression of miRNAs contribute to the development of different pathologies, including neoplastic diseases. Imbalance of intestinal microbiota due to diet is primary associated with the development of colorectal cancer as well as other types of cancers. In the present work we summarize current knowledge with particular emphasis on diet-microbiota-miRNAs axis and its relation to the development of colorectal cancer.

scholarly journals Systematic discovery of endogenous human ribonucleoprotein complexes

2018 ◽  
Author(s):  
Anna L. Mallam ◽  
Wisath Sae-Lee ◽  
Jeffrey M. Schaub ◽  
Fan Tu ◽  
Anna Battenhouse ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Complexes ◽  
Embryonic Stem ◽  
Human Protein ◽  
Disease States ◽  
Ribonucleoprotein Complexes ◽  
Associated Proteins ◽  
Domains Of Life ◽  
Factor C

AbstractRNA-binding proteins (RBPs) play essential roles in biology and are frequently associated with human disease. While recent studies have systematically identified individual RBPs, their higher order assembly intoRibonucleoprotein (RNP) complexes has not been systematically investigated. Here, we describe a proteomics method for systematic identification of RNP complexes in human cells. We identify 1,428 protein complexes that associate with RNA, indicating that over 20% of known human protein complexes contain RNA. To explore the role of RNA in the assembly of each complex, we identify complexes that dissociate, change composition, or form stable protein-only complexes in the absence of RNA. Importantly, these data also provide specific novel insights into the function of well-studied protein complexes not previously known to associate with RNA, including replication factor C (RFC) and cytokinetic centralspindlin complex. Finally, we use our method to systematically identify cell-type specific RNA-associated proteins in mouse embryonic stem cells. We distribute these data as a resource, rna.MAP (rna.proteincomplexes.org) which provides a comprehensive dataset for the study of RNA-associated protein complexes. Our system thus provides a novel methodology for further explorations across human tissues and disease states, as well as throughout all domains of life.SummaryAn exploration of human protein complexes in the presence and absence of RNA reveals endogenous ribonucleoprotein complexes

Unique Archaeal Small RNAs

2018 ◽  
Vol 52 (1) ◽  
pp. 465-487 ◽  
Author(s):  
José Vicente Gomes-Filho ◽  
Michael Daume ◽  
Lennart Randau
Keyword(s):  
Noncoding Rna ◽  
Genome Rearrangement ◽  
Rna Binding ◽  
Elevated Temperatures ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Extreme Environments ◽  
Noncoding Rnas ◽  
Hyperthermophilic Archaea ◽  
Rna Modification

Advances in genome-wide sequence technologies allow for detailed insights into the complexity of RNA landscapes of organisms from all three domains of life. Recent analyses of archaeal transcriptomes identified interaction and regulation networks of noncoding RNAs in this understudied domain. Here, we review current knowledge of small, noncoding RNAs with important functions for the archaeal lifestyle, which often requires adaptation to extreme environments. One focus is RNA metabolism at elevated temperatures in hyperthermophilic archaea, which reveals elevated amounts of RNA-guided RNA modification and virus defense strategies. Genome rearrangement events result in unique fragmentation patterns of noncoding RNA genes that require elaborate maturation pathways to yield functional transcripts. RNA-binding proteins, e.g., L7Ae and LSm, are important for many posttranscriptional control functions of RNA molecules in archaeal cells. We also discuss recent insights into the regulatory potential of their noncoding RNA partners.

scholarly journals A Single Amide Linkage in the Passenger Strand Suppresses Its Activity and Enhances Guide Strand Targeting of siRNAs

2018 ◽  
Vol 13 (3) ◽  
pp. 533-536 ◽  
Author(s):  
Travis Hardcastle ◽  
Irina Novosjolova ◽  
Venubabu Kotikam ◽  
Samwel K. Cheruiyot ◽  
Daniel Mutisya ◽  
...  
Keyword(s):  
Guide Strand ◽  
Amide Linkage ◽  
Passenger Strand

The human cortical autonomic network and volitional exercise in health and disease

2018 ◽  
Vol 43 (11) ◽  
pp. 1122-1130 ◽  
Author(s):  
Baraa K. Al-Khazraji ◽  
J. Kevin Shoemaker
Keyword(s):  
Current Knowledge ◽  
Insular Cortex ◽  
Cardiovascular Control ◽  
Anterior Cingulate ◽  
Disease States ◽  
Autonomic Activation ◽  
Imaging Research ◽  
Health And Disease ◽  
Cortical Regions

The autonomic nervous system elicits continuous beat-by-beat homeostatic adjustments to cardiovascular control. These modifications are mediated by sensory inputs (e.g., baroreceptors, metaboreceptors, pulmonary, thermoreceptors, and chemoreceptors afferents), integration at the brainstem control centres (i.e., medulla), and efferent autonomic neural outputs (e.g., spinal, preganglionic, and postganglionic pathways). However, extensive electrical stimulation and functional imaging research show that the brain’s higher cortical regions (e.g., insular cortex, medial prefrontal cortex, anterior cingulate cortex) partake in homeostatic regulation of the cardiovascular system at rest and during exercise. We now appreciate that these cortical areas form a network, namely the “cortical autonomic network” (CAN), which operate as part of a larger central autonomic network comprising 2-way communication of cortical and subcortical areas to exert autonomic influence. Interestingly, differential patterns of CAN activity and ensuing cardiovascular control are present in disease states, thereby highlighting the importance of considering the role of CAN as an integral aspect of cardiovascular regulation in health and disease. This review discusses current knowledge on human cortical autonomic activation during volitional exercise, and the role of exercise training on this activation in both health and disease.

The expanding world of metabolic enzymes moonlighting as RNA binding proteins

2021 ◽  
Author(s):  
Nicole J. Curtis ◽  
Constance J. Jeffery
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Molecular Structures ◽  
Intermediary Metabolism ◽  
The Many ◽  
And Function

RNA binding proteins play key roles in many aspects of RNA metabolism and function, including splicing, transport, translation, localization, stability and degradation. Within the past few years, proteomics studies have identified dozens of enzymes in intermediary metabolism that bind to RNA. The wide occurrence and conservation of RNA binding ability across distant branches of the evolutionary tree suggest that these moonlighting enzymes are involved in connections between intermediary metabolism and gene expression that comprise far more extensive regulatory networks than previously thought. There are many outstanding questions about the molecular structures and mechanisms involved, the effects of these interactions on enzyme and RNA functions, and the factors that regulate the interactions. The effects on RNA function are likely to be wider than regulation of translation, and some enzyme–RNA interactions have been found to regulate the enzyme's catalytic activity. Several enzyme–RNA interactions have been shown to be affected by cellular factors that change under different intracellular and environmental conditions, including concentrations of substrates and cofactors. Understanding the molecular mechanisms involved in the interactions between the enzymes and RNA, the factors involved in regulation, and the effects of the enzyme–RNA interactions on both the enzyme and RNA functions will lead to a better understanding of the role of the many newly identified enzyme–RNA interactions in connecting intermediary metabolism and gene expression.

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