scholarly journals The Cellular Functions and Molecular Mechanisms of G-Quadruplex Unwinding Helicases in Humans

2021 ◽  
Vol 8 ◽  
Author(s):  
Yang Liu ◽  
Xinting Zhu ◽  
Kejia Wang ◽  
Bo Zhang ◽  
Shuyi Qiu
Keyword(s):  
Molecular Mechanisms ◽  
Secondary Structures ◽  
Biological Processes ◽  
Cellular Functions ◽  
General Introduction ◽  
Rna Sequences ◽  
Study Methods ◽  
G Quadruplex ◽  
And Function

G-quadruplexes (G4s) are stable non-canonical secondary structures formed by G-rich DNA or RNA sequences. They play various regulatory roles in many biological processes. It is commonly agreed that G4 unwinding helicases play key roles in G4 metabolism and function, and these processes are closely related to physiological and pathological processes. In recent years, more and more functional and mechanistic details of G4 helicases have been discovered; therefore, it is necessary to carefully sort out the current research efforts. Here, we provide a systematic summary of G4 unwinding helicases from the perspective of functions and molecular mechanisms. First, we provide a general introduction about helicases and G4s. Next, we comprehensively summarize G4 unfolding helicases in humans and their proposed cellular functions. Then, we review their study methods and molecular mechanisms. Finally, we share our perspective on further prospects. We believe this review will provide opportunities for researchers to reach the frontiers in the functions and molecular mechanisms of human G4 unwinding helicases.

scholarly journals New gene discoveries in skeletal diseases with short stature

2021 ◽  
Author(s):  
Alice Costantini ◽  
Mari H Muurinen ◽  
Outi Mäkitie
Keyword(s):  
Short Stature ◽  
Molecular Mechanisms ◽  
Bone Growth ◽  
Massively Parallel Sequencing ◽  
Matrix Composition ◽  
Biological Processes ◽  
Novel Gene ◽  
Genetic Mechanisms ◽  
New Gene ◽  
And Function

In the last decade, the widespread use of massively-parallel sequencing has considerably boosted the number of novel gene discoveries in monogenic skeletal diseases with short stature. Defects in genes playing a role in the maintenance and function of the growth plate, the site of longitudinal bone growth, are a well-known cause of skeletal diseases with short stature. However, several genes involved in extracellular matrix composition or maintenance as well as genes partaking in various biological processes have also been characterized. This review aims to describe the latest genetic findings in spondyloepiphyseal and spondyloepimetaphyseal dysplasias and in some monogenic forms of isolated short stature. Strategies on how to successfully characterize novel skeletal phenotypes with short stature and genetic approaches to detect and validate novel gene-disease correlations will be discussed in detail. Finally, novel genetic mechanisms in the field of skeletal diseases, including variants affecting miRNAs and disrupting the chromatin structure, will be described. In summary, we discuss the latest gene discoveries underlying skeletal diseases with short stature and emphasize the importance of characterizing novel molecular mechanisms for genetic counseling, optimal management of the disease and for therapeutic innovations.

scholarly journals The Expression and Function of Circadian Rhythm Genes in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yanan Jiang ◽  
Xiuyun Shen ◽  
Moyondafoluwa Blessing Fasae ◽  
Fengnan Zhi ◽  
Lu Chai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Pathogenic Mechanism ◽  
Research Progress ◽  
Biological Processes ◽  
And Function ◽  
Novel Therapeutic

Hepatocellular carcinoma (HCC) is among the most common and lethal form of cancer worldwide. However, its diagnosis and treatment are still dissatisfactory, due to limitations in the understanding of its pathogenic mechanism. Therefore, it is important to elucidate the molecular mechanisms and identify novel therapeutic targets for HCC. Circadian rhythm-related genes control a variety of biological processes. These genes play pivotal roles in the initiation and progression of HCC and are potential diagnostic markers and therapeutic targets. This review gives an update on the research progress of circadian rhythms, their effects on the initiation, progression, and prognosis of HCC, in a bid to provide new insights for the research and treatment of HCC.

scholarly journals The effect of hairpin loop on the structure and gene expression activity of the long-loop G-quadruplex

2021 ◽  
Author(s):  
Subramaniyam Ravichandran ◽  
Maria Razzaq ◽  
Nazia Parveen ◽  
Ambarnil Ghosh ◽  
Kyeong Kyu Kim
Keyword(s):  
Gene Expression ◽  
Rna Structure ◽  
Biological Significance ◽  
Cellular Functions ◽  
Hairpin Loops ◽  
G Quadruplex ◽  
Reporter Assays ◽  
Expression Activity ◽  
The Stability ◽  
And Function

Abstract G-quadruplex (G4), a four-stranded DNA or RNA structure containing stacks of guanine tetrads, plays regulatory roles in many cellular functions. So far, conventional G4s containing loops of 1–7 nucleotides have been widely studied. Increasing experimental evidence suggests that unconventional G4s, such as G4s containing long loops (long-loop G4s), play a regulatory role in the genome by forming a stable structure. Other secondary structures such as hairpins in the loop might thus contribute to the stability of long-loop G4s. Therefore, investigation of the effect of the hairpin-loops on the structure and function of G4s is required. In this study, we performed a systematic biochemical investigation of model G4s containing long loops with various sizes and structures. We found that the long-loop G4s are less stable than conventional G4s, but their stability increased when the loop forms a hairpin (hairpin-G4). We also verified the biological significance of hairpin-G4s by showing that hairpin-G4s present in the genome also form stable G4s and regulate gene expression as confirmed by in cellulo reporter assays. This study contributes to expanding the scope and diversity of G4s, thus facilitating future studies on the role of G4s in the human genome.

scholarly journals Recent progress in research on molecular mechanisms of autophagy in the heart

2015 ◽  
Vol 308 (4) ◽  
pp. H259-H268 ◽  
Author(s):  
Yasuhiro Maejima ◽  
Yun Chen ◽  
Mitsuaki Isobe ◽  
Åsa B. Gustafsson ◽  
Richard N. Kitsis ◽  
...  
Keyword(s):  
Heart Disease ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Degradation Process ◽  
Structure And Function ◽  
Cellular Functions ◽  
Evolutionarily Conserved ◽  
And Function ◽  
Cellular Dysfunction

Dysregulation of autophagy, an evolutionarily conserved process for degradation of long-lived proteins and organelles, has been implicated in the pathogenesis of human disease. Recent research has uncovered pathways that control autophagy in the heart and molecular mechanisms by which alterations in this process affect cardiac structure and function. Although initially thought to be a nonselective degradation process, autophagy, as it has become increasingly clear, can exhibit specificity in the degradation of molecules and organelles, such as mitochondria. Furthermore, it has been shown that autophagy is involved in a wide variety of previously unrecognized cellular functions, such as cell death and metabolism. A growing body of evidence suggests that deviation from appropriate levels of autophagy causes cellular dysfunction and death, which in turn leads to heart disease. Here, we review recent advances in understanding the role of autophagy in heart disease, highlight unsolved issues, and discuss the therapeutic potential of modulating autophagy in heart disease.

scholarly journals Conformation of G-quadruplex Controlled by Click Reaction

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4339
Author(s):  
Chao-Da Xiao ◽  
Zhi-Yong He ◽  
Chuan-Xin Guo ◽  
Xiang-Chun Shen ◽  
Yan Xu
Keyword(s):  
Click Chemistry ◽  
Dna Sequence ◽  
Click Reaction ◽  
Secondary Structures ◽  
Biological Processes ◽  
Biological Importance ◽  
Intense Fluorescence ◽  
G Quadruplex ◽  
First Time

G-quadruplexes are non-canonical four stranded secondary structures possessing great biological importance. Controlling G-quadruplex conformation for further regulating biological processes is both exciting and challenging. In this study, we described a method for regulating G-quadruplex conformation by click chemistry for the first time. 8-ethynyl-2′-deoxyguanosine was synthesized and incorporated into a 12-nt telomere DNA sequence. Such a sequence, at first, formed mixed parallel/anti-parallel G-quadruplexes, while it changed to anti-parallel after reaction with azidobenzene. Meanwhile, the click reaction can give the sequence intense fluorescence.

scholarly journals On the Wrong Track: Alterations of Ciliary Transport in Inherited Retinal Dystrophies

2021 ◽  
Vol 9 ◽  
Author(s):  
Laura Sánchez-Bellver ◽  
Vasileios Toulis ◽  
Gemma Marfany
Keyword(s):  
Retinal Degeneration ◽  
Outer Segment ◽  
Molecular Mechanisms ◽  
Photoreceptor Cells ◽  
Cellular Functions ◽  
Inherited Disorders ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
Elevated Protein ◽  
And Function

Ciliopathies are a group of heterogeneous inherited disorders associated with dysfunction of the cilium, a ubiquitous microtubule-based organelle involved in a broad range of cellular functions. Most ciliopathies are syndromic, since several organs whose cells produce a cilium, such as the retina, cochlea or kidney, are affected by mutations in ciliary-related genes. In the retina, photoreceptor cells present a highly specialized neurosensory cilium, the outer segment, stacked with membranous disks where photoreception and phototransduction occurs. The daily renewal of the more distal disks is a unique characteristic of photoreceptor outer segments, resulting in an elevated protein demand. All components necessary for outer segment formation, maintenance and function have to be transported from the photoreceptor inner segment, where synthesis occurs, to the cilium. Therefore, efficient transport of selected proteins is critical for photoreceptor ciliogenesis and function, and any alteration in either cargo delivery to the cilium or intraciliary trafficking compromises photoreceptor survival and leads to retinal degeneration. To date, mutations in more than 100 ciliary genes have been associated with retinal dystrophies, accounting for almost 25% of these inherited rare diseases. Interestingly, not all mutations in ciliary genes that cause retinal degeneration are also involved in pleiotropic pathologies in other ciliated organs. Depending on the mutation, the same gene can cause syndromic or non-syndromic retinopathies, thus emphasizing the highly refined specialization of the photoreceptor neurosensory cilia, and raising the possibility of photoreceptor-specific molecular mechanisms underlying common ciliary functions such as ciliary transport. In this review, we will focus on ciliary transport in photoreceptor cells and discuss the molecular complexity underpinning retinal ciliopathies, with a special emphasis on ciliary genes that, when mutated, cause either syndromic or non-syndromic retinal ciliopathies.

scholarly journals Mechanisms underlying gut microbiota–host interactions in insects

2021 ◽  
Vol 224 (2) ◽  
pp. jeb207696 ◽  
Author(s):  
Konstantin Schmidt ◽  
Philipp Engel
Keyword(s):  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Molecular Processes ◽  
General Introduction ◽  
Host Interactions ◽  
Host Nutrition ◽  
Insect Gut ◽  
Almost All ◽  
And Function

ABSTRACTInsects are the most diverse group of animals and colonize almost all environments on our planet. This diversity is reflected in the structure and function of the microbial communities inhabiting the insect digestive system. As in mammals, the gut microbiota of insects can have important symbiotic functions, complementing host nutrition, facilitating dietary breakdown or providing protection against pathogens. There is an increasing number of insect models that are experimentally tractable, facilitating mechanistic studies of gut microbiota–host interactions. In this Review, we will summarize recent findings that have advanced our understanding of the molecular mechanisms underlying the symbiosis between insects and their gut microbiota. We will open the article with a general introduction to the insect gut microbiota and then turn towards the discussion of particular mechanisms and molecular processes governing the colonization of the insect gut environment as well as the diverse beneficial roles mediated by the gut microbiota. The Review highlights that, although the gut microbiota of insects is an active field of research with implications for fundamental and applied science, we are still in an early stage of understanding molecular mechanisms. However, the expanding capability to culture microbiomes and to manipulate microbe–host interactions in insects promises new molecular insights from diverse symbioses.

scholarly journals Pathophysiological Role of K2P Channels in Human Diseases

2021 ◽  
Vol 55 (S3) ◽  
pp. 65-86
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Ion Homeostasis ◽  
Human Diseases ◽  
Cellular Functions ◽  
Aberrant Expression ◽  
K2p Channels ◽  
And Function

The family of two-pore domain potassium (K2P) channels is critically involved in central cellular functions such as ion homeostasis, cell development, and excitability. K2P channels are widely expressed in different human cell types and organs. It is therefore not surprising that aberrant expression and function of K2P channels are related to a spectrum of human diseases, including cancer, autoimmune, CNS, cardiovascular, and urinary tract disorders. Despite homologies in structure, expression, and stimulus, the functional diversity of K2P channels leads to heterogeneous influences on human diseases. The role of individual K2P channels in different disorders depends on expression patterns and modulation in cellular functions. However, an imbalance of potassium homeostasis and action potentials contributes to most disease pathologies. In this review, we provide an overview of current knowledge on the role of K2P channels in human diseases. We look at altered channel expression and function, the potential underlying molecular mechanisms, and prospective research directions in the field of K2P channels.

scholarly journals lncRNAs in development and differentiation: from sequence motifs to functional characterization

Development ◽  
2021 ◽  
Vol 148 (1) ◽  
pp. dev182741
Author(s):  
Florian Constanty ◽  
Alena Shkumatava
Keyword(s):  
Molecular Mechanisms ◽  
Functional Characterization ◽  
Sequence Motifs ◽  
Cellular Functions ◽  
Rna Motifs ◽  
Rna Sequences ◽  
Conserved Sequence ◽  
Interaction Partners ◽  
Sequence Elements ◽  
Development And Differentiation

ABSTRACTThe number of long noncoding RNAs (lncRNAs) with characterized developmental and cellular functions continues to increase, but our understanding of the molecular mechanisms underlying lncRNA functions, and how they are dictated by RNA sequences, remains limited. Relatively short, conserved sequence motifs embedded in lncRNA transcripts are often important determinants of lncRNA localization, stability and interactions. Identifying such RNA motifs remains challenging due to the substantial length of lncRNA transcripts and the rapid evolutionary turnover of lncRNA sequences. Nevertheless, the recent discovery of specific RNA elements, together with their experimental interrogation, has enabled the first step in classifying heterogeneous lncRNAs into sub-groups with similar molecular mechanisms and functions. In this Review, we focus on lncRNAs with roles in development, cell differentiation and normal physiology in vertebrates, and we discuss the sequence elements defining their functions. We also summarize progress on the discovery of regulatory RNA sequence elements, as well as their molecular functions and interaction partners.

scholarly journals Structure of two G-quadruplexes in equilibrium in the KRAS promoter

2020 ◽  
Vol 48 (16) ◽  
pp. 9336-9345 ◽  
Author(s):  
Julien Marquevielle ◽  
Coralie Robert ◽  
Olivier Lagrabette ◽  
Mona Wahid ◽  
Anne Bourdoncle ◽  
...  
Keyword(s):  
Secondary Structures ◽  
Alternative Strategy ◽  
Biological Processes ◽  
Rna Sequences ◽  
Its Gene

Abstract KRAS is one of the most mutated oncogenes and still considered an undruggable target. An alternative strategy would consist in targeting its gene rather than the protein, specifically the formation of G-quadruplexes (G4) in its promoter. G4 are secondary structures implicated in biological processes, which can be formed among G-rich DNA (or RNA) sequences. Here we have studied the major conformations of the commonly known KRAS 32R, or simply 32R, a 32 residue sequence within the KRAS Nuclease Hypersensitive Element (NHE) region. We have determined the structure of the two major stable conformers that 32R can adopt and which display slow equilibrium (>ms) with each other. By using different biophysical methods, we found that the nucleotides G9, G25, G28 and G32 are particularly implicated in the exchange between these two conformations. We also showed that a triad at the 3′ end further stabilizes one of the G4 conformations, while the second conformer remains more flexible and less stable.

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