scholarly journals Cytoplasmic RNA Granules in Somatic Maintenance

Gerontology ◽  
2018 ◽  
Vol 64 (5) ◽  
pp. 485-494 ◽  
Author(s):  
Ossama Moujaber ◽  
Ursula Stochaj
Keyword(s):  
Somatic Cell ◽  
Current Knowledge ◽  
Physiological State ◽  
Physiological Role ◽  
Cellular Functions ◽  
Rna Granules ◽  
Cytoplasmic Rna ◽  
Open Questions ◽  
And Function ◽  
The Impact

Cytoplasmic RNA granules represent subcellular compartments that are enriched in protein-bound RNA species. RNA granules are produced by evolutionary divergent eukaryotes, including yeast, mammals, and plants. The functions of cytoplasmic RNA granules differ widely. They are dictated by the cell type and physiological state, which in turn is determined by intrinsic cell properties and environmental factors. RNA granules provide diverse cellular functions. However, all of the granules contribute to aspects of RNA metabolism. This is exemplified by transcription, RNA storage, silencing, and degradation, as well as mRNP remodeling and regulated translation. Several forms of cytoplasmic mRNA granules are linked to normal physiological processes. For instance, they may coordinate protein synthesis and thereby serve as posttranscriptional “operons”. RNA granules also participate in cytoplasmic mRNA trafficking, a process particularly well understood for neurons. Many forms of RNA granules support the preservation of somatic cell performance under normal and stress conditions. On the other hand, severe insults or disease can cause the formation and persistence of RNA granules that contribute to cellular dysfunction, especially in the nervous system. Neurodegeneration and many other diseases linked to RNA granules are associated with aging. Nevertheless, information related to the impact of aging on the various types of RNA granules is presently very limited. This review concentrates on cytoplasmic RNA granules and their role in somatic cell maintenance. We summarize the current knowledge on different types of RNA granules in the cytoplasm, their assembly and function under normal, stress, or disease conditions. Specifically, we discuss processing bodies, neuronal granules, stress granules, and other less characterized cytoplasmic RNA granules. Our focus is primarily on mammalian and yeast models, because they have been critical to unravel the physiological role of various RNA granules. RNA granules in plants and pathogens are briefly described. We conclude our viewpoint by summarizing the emerging concepts for RNA granule biology and the open questions that need to be addressed in future studies.

The DEAH helicase DHX36 and its role in G-quadruplex-dependent processes

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Philipp Schult ◽  
Katrin Paeschke
Keyword(s):  
Current Knowledge ◽  
Future Research ◽  
Transcriptional Level ◽  
Cellular Functions ◽  
Multiple Functions ◽  
Open Questions ◽  
G Quadruplex ◽  
Cellular Pathways ◽  
Nucleic Acid Structures ◽  
Dependent Processes

AbstractDHX36 is a member of the DExD/H box helicase family, which comprises a large number of proteins involved in various cellular functions. Recently, the function of DHX36 in the regulation of G-quadruplexes (G4s) was demonstrated. G4s are alternative nucleic acid structures, which influence many cellular pathways on a transcriptional and post-transcriptional level. In this review we provide an overview of the current knowledge about DHX36 structure, substrate specificity, and mechanism of action based on the available models and crystal structures. Moreover, we outline its multiple functions in cellular homeostasis, immunity, and disease. Finally, we discuss the open questions and provide potential directions for future research.

scholarly journals Insights into the Cellular and Molecular Mechanisms That Govern the Fracture-Healing Process: A Narrative Review

2021 ◽  
Vol 10 (16) ◽  
pp. 3554
Author(s):  
Dionysios J. Papachristou ◽  
Stavros Georgopoulos ◽  
Peter V. Giannoudis ◽  
Elias Panagiotopoulos
Keyword(s):  
Fracture Healing ◽  
Bone Repair ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Healing Process ◽  
Bone Architecture ◽  
Multi Stage ◽  
Stage Process ◽  
And Function ◽  
The Impact

Fracture-healing is a complex multi-stage process that usually progresses flawlessly, resulting in restoration of bone architecture and function. Regrettably, however, a considerable number of fractures fail to heal, resulting in delayed unions or non-unions. This may significantly impact several aspects of a patient’s life. Not surprisingly, in the past few years, a substantial amount of research and number of clinical studies have been designed, aiming at shedding light into the cellular and molecular mechanisms that regulate fracture-healing. Herein, we present the current knowledge on the pathobiology of the fracture-healing process. In addition, the role of skeletal cells and the impact of marrow adipose tissue on bone repair is discussed. Unveiling the pathogenetic mechanisms that govern the fracture-healing process may lead to the development of novel, smarter, and more effective therapeutic strategies for the treatment of fractures, especially of those with large bone defects.

scholarly journals POLIII-derived non-coding RNAs acting as scaffolds and decoys

2019 ◽  
Vol 11 (10) ◽  
pp. 880-885 ◽  
Author(s):  
Hendrik Täuber ◽  
Stefan Hüttelmaier ◽  
Marcel Köhn
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Cellular Functions ◽  
Control Of Gene Expression ◽  
Ribonucleoprotein Complexes ◽  
Small Ncrnas ◽  
Non Coding Rnas ◽  
And Function

Abstract A large variety of eukaryotic small structured POLIII-derived non-coding RNAs (ncRNAs) have been described in the past. However, for only few, e.g. 7SL and H1/MRP families, cellular functions are well understood. For the vast majority of these transcripts, cellular functions remain unknown. Recent findings on the role of Y RNAs and other POLIII-derived ncRNAs suggest an evolutionarily conserved function of these ncRNAs in the assembly and function of ribonucleoprotein complexes (RNPs). These RNPs provide cellular `machineries’, which are essential for guiding the fate and function of a variety of RNAs. In this review, we summarize current knowledge on the role of POLIII-derived ncRNAs in the assembly and function of RNPs. We propose that these ncRNAs serve as scaffolding factors that `chaperone’ RNA-binding proteins (RBPs) to form functional RNPs. In addition or associated with this role, some small ncRNAs act as molecular decoys impairing the RBP-guided control of RNA fate by competing with other RNA substrates. This suggests that POLIII-derived ncRNAs serve essential and conserved roles in the assembly of larger RNPs and thus the control of gene expression by indirectly guiding the fate of mRNAs and lncRNAs.

scholarly journals The Mysteries around the BCL-2 Family Member BOK

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1638
Author(s):  
Raed Shalaby ◽  
Hector Flores-Romero ◽  
Ana J. García-Sáez
Keyword(s):  
Family Member ◽  
Cell Fate ◽  
Current Knowledge ◽  
Structural Features ◽  
Special Focus ◽  
Cellular Functions ◽  
Open Questions ◽  
Apoptotic Protein ◽  
Evolutionarily Conserved ◽  
Apoptosis Regulation

BOK is an evolutionarily conserved BCL-2 family member that resembles the apoptotic effectors BAK and BAX in sequence and structure. Based on these similarities, BOK has traditionally been classified as a BAX-like pro-apoptotic protein. However, the mechanism of action and cellular functions of BOK remains controversial. While some studies propose that BOK could replace BAK and BAX to elicit apoptosis, others attribute to this protein an indirect way of apoptosis regulation. Adding to the debate, BOK has been associated with a plethora of non-apoptotic functions that makes this protein unpredictable when dictating cell fate. Here, we compile the current knowledge and open questions about this paradoxical protein with a special focus on its structural features as the key aspect to understand BOK biological functions.

scholarly journals Obstructive Sleep Apnea in Neurodegenerative Disorders: Current Evidence in Support of Benefit from Sleep Apnea Treatment

2020 ◽  
Vol 9 (2) ◽  
pp. 297 ◽  
Author(s):  
Annie C. Lajoie ◽  
Anne-Louise Lafontaine ◽  
R. John Kimoff ◽  
Marta Kaminska
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Current Knowledge ◽  
Upper Airway ◽  
Current Evidence ◽  
Obstructive Sleep ◽  
Intermittent Hypoxemia ◽  
And Function ◽  
The Impact ◽  
Sleep Apnea Treatment

Obstructive sleep apnea (OSA) is a prevalent disorder characterized by recurrent upper airway obstruction during sleep resulting in intermittent hypoxemia and sleep fragmentation. Research has recently increasingly focused on the impact of OSA on the brain’s structure and function, in particular as this relates to neurodegenerative diseases. This article reviews the links between OSA and neurodegenerative disease, focusing on Parkinson’s disease, including proposed pathogenic mechanisms and current knowledge on the effects of treatment.

scholarly journals Aberrant CXCR4 Signaling at Crossroad of WHIM Syndrome and Waldenstrom’s Macroglobulinemia

2020 ◽  
Vol 21 (16) ◽  
pp. 5696 ◽  
Author(s):  
Samantha Milanesi ◽  
Massimo Locati ◽  
Elena Monica Borroni
Keyword(s):  
Current Knowledge ◽  
Biochemical Properties ◽  
Response To Therapy ◽  
Cxcr4 Signaling ◽  
Whim Syndrome ◽  
Open Questions ◽  
Congenital Immunodeficiency ◽  
Pleiotropic Functions ◽  
The Impact ◽  
Significant Attention

Given its pleiotropic functions, including its prominent role in inflammation, immune responses and cancer, the C-X-C chemokine receptor type 4 (CXCR4) has gained significant attention in recent years and has become a relevant target in drug development. Although the signaling properties of CXCR4 have been extensively studied, several aspects deserve deeper investigations. Mutations in the C-term tail of the CXCR4 gene cause WHIM syndrome, a rare congenital immunodeficiency associated by chronic leukopenia. Similar mutations have also been recently identified in 30% of patients affected by Waldenstrom’s macroglobulinaemia, a B-cell neoplasia with bone marrow accumulation of malignant cells. An ample body of work has been generated to define the impact of WHIM mutations on CXCR4 signaling properties and evaluate their role on pathogenesis, diagnosis, and response to therapy, although the identity of disease-causing signaling pathways and their relevance for disease development in different genetic variants are still open questions. This review discusses the current knowledge on biochemical properties of CXCR4 mutations to identify their prototypic signaling profile potentially useful to highlighting novel opportunities for therapeutic intervention.

scholarly journals π-Excess-aromatic and non-aromatic 1,3-azaphospholes – impact of annulation and multiple reactivity

2019 ◽  
Vol 91 (5) ◽  
pp. 761-771
Author(s):  
Joachim W. Heinicke
Keyword(s):  
Current Knowledge ◽  
Substituent Effects ◽  
Open Questions ◽  
The Impact ◽  
Aromatic Stabilization

Abstract Syntheses, properties, structure aspects and reactivity of non- and aromatically carbo- and heterocyclic annulated 1H- and 3H-1,3-azaphospholes are compared to illuminate the impact of annulation, substituent effects, aromatic stabilization and π-excess at phosphorus of the 1H-isomers, to demonstrate the current knowledge and open questions in this field of research.

scholarly journals Janus-faced spatacsin (SPG11): involvement in neurodevelopment and multisystem neurodegeneration

Brain ◽  
2020 ◽  
Vol 143 (8) ◽  
pp. 2369-2379
Author(s):  
Tatyana Pozner ◽  
Martin Regensburger ◽  
Tobias Engelhorn ◽  
Jürgen Winkler ◽  
Beate Winner
Keyword(s):  
Clinical Symptoms ◽  
Current Knowledge ◽  
Clinical Manifestations ◽  
Lower Limbs ◽  
Pathogenic Variants ◽  
Structural Abnormalities ◽  
Neuronal Systems ◽  
And Function ◽  
The Impact

Abstract Hereditary spastic paraplegia (HSP) is a heterogeneous group of rare motor neuron disorders characterized by progressive weakness and spasticity of the lower limbs. HSP type 11 (SPG11-HSP) is linked to pathogenic variants in the SPG11 gene and it represents the most frequent form of complex autosomal recessive HSP. The majority of SPG11-HSP patients exhibit additional neurological symptoms such as cognitive decline, thin corpus callosum, and peripheral neuropathy. Yet, the mechanisms of SPG11-linked spectrum diseases are largely unknown. Recent findings indicate that spatacsin, the 280 kDa protein encoded by SPG11, may impact the autophagy-lysosomal machinery. In this update, we summarize the current knowledge of SPG11-HSP. In addition to clinical symptoms and differential diagnosis, our work aims to link the different clinical manifestations with the respective structural abnormalities and cellular in vitro phenotypes. Moreover, we describe the impact of localization and function of spatacsin in different neuronal systems. Ultimately, we propose a model in which spatacsin bridges between neurodevelopmental and neurodegenerative phenotypes of SPG11-linked disorders.

scholarly journals GDNF and protection of adult central catecholaminergic neurons

2011 ◽  
Vol 46 (3) ◽  
pp. R83-R92 ◽  
Author(s):  
Alberto Pascual ◽  
María Hidalgo-Figueroa ◽  
Raquel Gómez-Díaz ◽  
José López-Barneo
Keyword(s):  
Current Knowledge ◽  
Physiological Role ◽  
Adult Brain ◽  
Peripheral Neurons ◽  
Central Neurons ◽  
Small Proteins ◽  
Therapeutic Tools ◽  
And Function ◽  
Catecholaminergic Cells

Neurotrophic factors are small proteins necessary for neuron survival and maintenance of phenotype. They are considered as promising therapeutic tools for neurodegenerative diseases. The glial cell line-derived neurotrophic factor (GDNF) protects catecholaminergic cells from toxic insults; thus, its potential therapeutic applicability in Parkinson's disease has been intensely investigated. In recent years, there have been major advances in the analysis of GDNF signaling pathways in peripheral neurons and embryonic dopamine mesencephalic cells. However, the actual physiological role of GDNF in maintaining catecholaminergic central neurons during adulthood is only starting to be unraveled, and the mechanisms whereby GDNF protects central brain neurons are poorly known. In this study, we review the current knowledge of GDNF expression, signaling, and function in adult brain, with special emphasis on the genetic animal models with deficiency in the GDNF-dependent pathways.

The influence of glucocorticoids on neuronal survival and synaptic function

2012 ◽  
Vol 3 (6) ◽  
pp. 495-504 ◽  
Author(s):  
Tadahiro Numakawa ◽  
Naoki Adachi ◽  
Misty Richards ◽  
Shuichi Chiba ◽  
Hiroshi Kunugi
Keyword(s):  
Current Knowledge ◽  
Neuronal Survival ◽  
Synaptic Function ◽  
Multiple Roles ◽  
Neuronal Populations ◽  
Animal Models Of Depression ◽  
The Central Nervous System ◽  
As Stress ◽  
And Function ◽  
The Impact

AbstractGlucocorticoids, recognized as stress-related steroid hormones secreted from adrenal glands, have multiple roles in brain function. The concentration of glucocorticoids is regulated by the hypothalamic-pituitary-adrenal axis, and chronically elevated levels of glucocorticoids are putatively involved in the pathophysiology of mental disorders, such as depression. As corticosteroids are also widely used as medical drugs (e.g., for chronic lung disease in infants), the developmental influence of glucocorticoids on neuronal survival and synaptic plasticity is a critical concern. Although many reports suggest a biological effect of glucocorticoids on neuronal populations of the central nervous system (CNS), some reports suggest a possibility that glial responses (including regulation of neurotrophic factor expression) to glucocorticoids are different from that of neurons. In the present review, we show an overview of the current knowledge concerning the impact of glucocorticoids on behavior in animal models of depression, and on cell survival and function in the CNS.

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