scholarly journals Dynamic landscape and evolution of m6A methylation in human

2020 ◽  
Vol 48 (11) ◽  
pp. 6251-6264 ◽  
Author(s):  
Hui Zhang ◽  
Xinrui Shi ◽  
Tao Huang ◽  
Xueni Zhao ◽  
Wanying Chen ◽  
...  
Keyword(s):  
Binding Sites ◽  
Rna Modification ◽  
Human Populations ◽  
Evolutionary Constraint ◽  
Cleavage Sites ◽  
Future Studies ◽  
Adult Tissues ◽  
Dynamic Landscape ◽  
Mrna Fate

Abstract m6A is a prevalent internal modification in mRNAs and has been linked to the diverse effects on mRNA fate. To explore the landscape and evolution of human m6A, we generated 27 m6A methylomes across major adult tissues. These data reveal dynamic m6A methylation across tissue types, uncover both broadly or tissue-specifically methylated sites, and identify an unexpected enrichment of m6A methylation at non-canonical cleavage sites. A comparison of fetal and adult m6A methylomes reveals that m6A preferentially occupies CDS regions in fetal tissues. Moreover, the m6A sub-motifs vary between fetal and adult tissues or across tissue types. From the evolutionary perspective, we uncover that the selection pressure on m6A sites varies and depends on their genic locations. Unexpectedly, we found that ∼40% of the 3′UTR m6A sites are under negative selection, which is higher than the evolutionary constraint on miRNA binding sites, and much higher than that on A-to-I RNA modification. Moreover, the recently gained m6A sites in human populations are clearly under positive selection and associated with traits or diseases. Our work provides a resource of human m6A profile for future studies of m6A functions, and suggests a role of m6A modification in human evolutionary adaptation and disease susceptibility.

scholarly journals Signatures of genetic variation in human microRNAs point to processes of positive selection related to population-specific disease risks

2021 ◽  
Author(s):  
Pablo Villegas Mirón ◽  
Alicia Gallego ◽  
Jaume Bertranpetit ◽  
Hafid Laayouni ◽  
Yolanda Espinosa-Parrilla
Keyword(s):  
Genetic Variation ◽  
Disease Risk ◽  
In Silico Analysis ◽  
Human Populations ◽  
Evolutionary Constraint ◽  
Seed Region ◽  
Specific Disease ◽  
A Minor ◽  
Diversity Profiles

The occurrence of natural variation in human microRNAs has been the focus of numerous studies during the last twenty years. Most of them have been dedicated to study the role of specific mutations in diseases, like cancer, while a minor fraction seek to analyse the diversity profiles of microRNAs in the genomes of human populations. In the present study we analyse the latest human microRNA annotations in the light of the most updated catalog of genetic variation provided by the 1000 Genomes Project. We show by means of the in silico analysis of noncoding variation of microRNAs that the level of evolutionary constraint of these sequences is governed by the interplay of different factors, like their evolutionary age or the genomic location where they emerged. The role of mutations in the shaping of microRNA-driven regulatory interactions is emphasized with the acknowledgement that, while the whole microRNA sequence is highly conserved, the seed region shows a pattern of higher genetic diversity that appears to be caused by the dramatic frequency shifts of a fraction of human microRNAs. We highlight the participation of these microRNAs in population-specific processes by identifying that not only the seed, but also the loop, are particularly differentiated regions among human populations. The quantitative computational comparison of signatures of population differentiation showed that candidate microRNAs with the largest differences are enriched in variants implicated in gene expression levels (eQTLs), selective sweeps and pathological processes. We explore the implication of these evolutionary-driven microRNAs and their SNPs in human diseases, such as different types of cancer, and discuss their role in population-specific disease risk.

Ghrelin and Cardiovasculature

2010 ◽  
Vol 06 ◽  
pp. 64
Author(s):  
Jörgen Isgaard ◽  
Keyword(s):  
Cardiovascular Disease ◽  
Binding Sites ◽  
Cardiovascular Effects ◽  
Inotropic Effects ◽  
Future Studies ◽  
Gh Secretion ◽  
Cardioprotective Effects ◽  
Therapeutic Tools

Apart from stimulating growth hormone (GH) secretion and a regulatory role for appetite and metabolism, it has become increasingly clear that GH secretagogues (GHS) and ghrelin exert a number of effects on the cardiovascular system. The main cardiovascular actions of GHS are possible inotropic effects, vasodilation, reported cardioprotective effects against ischaemia andin vitroeffects on cardiomyocytes involving cell proliferation and antiapoptotic actions. An interesting and intriguing feature of the cardiovascular effects of GHS is that they may be exerted directly on the heart and vasculature rather than being mediated by GH. Evidence to suggest this is the finding of GHS binding sites on cardiomyocytes and the fact that some of the effects of GHS can be expressed also in the absence of GH. Although these results offer interesting possibilities for ghrelin and/or GHS to be used as therapeutic tools in cardiovascular disease, larger clinical trials in this area are still lacking. Future studies aiming at evaluating a role of GHS and ghrelin in the treatment of cardiovascular disease are warranted.

scholarly journals Assessing the Potential Interactions between Cellular miRNA and Arboviral Genomic RNA in the Yellow Fever Mosquito, Aedes aegypti

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 540 ◽  
Author(s):  
Pei-Shi Yen ◽  
Chun-Hong Chen ◽  
Vattipally Sreenu ◽  
Alain Kohl ◽  
Anna-Bella Failloux
Keyword(s):  
Aedes Aegypti ◽  
Binding Sites ◽  
Experimental Validation ◽  
P Element ◽  
Rna Structures ◽  
Future Studies ◽  
Genomic Analyses ◽  
Interfering Rna ◽  
Potential Interactions

Although the role of exogenous small interfering RNA (siRNA) and P-element induced wimpy testis (PIWI)-interacting RNA (piRNA) pathways in mosquito antiviral immunity is increasingly better understood, there is still little knowledge regarding the role of mosquito cellular microRNA (miRNA). Identifying direct interactions between the mosquito miRNAs and the RNA genome of arboviruses and choosing the relevant miRNA candidates to explore resulting antiviral mechanisms are critical. Here, we carried out genomic analyses to identify Aedes aegypti miRNAs that potentially interact with various lineages and genotypes of chikungunya, dengue, and Zika viruses. By using prediction tools with distinct algorithms, several miRNA binding sites were commonly found within different genotypes/and or lineages of each arbovirus. We further analyzed those miRNAs that could target more than one arbovirus, required a low energy threshold to form miRNA-viralRNA (vRNA) complexes, and predicted potential RNA structures using RNAhybrid software. We predicted miRNA candidates that might participate in regulating arboviral replication in Ae. aegypti. Even without any experimental validation, which should be done as a next step, this study can shed further light on the role of miRNA in mosquito innate immunity and targets for future studies.

scholarly journals Signatures of Genetic Variation in Human microRNAs Point to Processes of Positive Selection and Population-specific Disease Risks

2021 ◽  
Author(s):  
Pablo Villegas-Mirón ◽  
Alcia Gallego ◽  
Jaume Bertranpetit ◽  
Hafid Laayouni ◽  
Yolanda Espinosa Parrilla
Keyword(s):  
Genetic Variation ◽  
Disease Risk ◽  
Human Populations ◽  
Evolutionary Constraint ◽  
Seed Region ◽  
Single Nucleotide Variants ◽  
Specific Disease ◽  
Genomic Location ◽  
A Minor

Abstract The occurrence of natural variation in human microRNAs has been the focus of numerous studies during the last twenty years. Most of them have been centered on the role of specific mutations in disease, while a minor proportion seek to analyse microRNA diversity in the genomes of human populations. We investigate the latest human microRNA annotations in the light of the most updated catalog of genetic variation provided by the 1000 Genomes Project. By means of the in silico analysis of microRNA variants we show that the level of evolutionary constraint of these sequences is governed by the interplay of different factors, like their evolutionary age or genomic location. The role of mutations in the shaping of microRNA-driven regulatory interactions is emphasized with the acknowledgement that, while the whole microRNA sequence is highly conserved, the seed region shows a pattern of higher genetic diversity that appears to be caused by the dramatic frequency shifts of a fraction of human microRNAs. We highlight the participation of these microRNAs in population-specific processes by identifying that not only the seed, but also the loop, are particularly differentiated regions among human populations. The quantitative computational comparison of signatures of population differentiation showed that candidate microRNAs with the largest differences are enriched in variants related to gene expression levels (eQTLs), selective sweeps and pathological processes. We explore the implication of these evolutionary-driven microRNAs and their single nucleotide variants in human diseases, such as different types of cancer, and discuss their role in population-specific disease risk.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

Motives for Social Isolation Following a Negative Emotional Episode

2018 ◽  
Vol 77 (3) ◽  
pp. 127-131
Author(s):  
Gérald Delelis ◽  
Véronique Christophe
Keyword(s):  
Social Isolation ◽  
Social Affiliation ◽  
Semantic Categorization ◽  
Future Studies ◽  
Cognitive Regulation ◽  
Emotional Event ◽  
Regulation Strategies ◽  
Emotional Events

Abstract. After experiencing an emotional event, people either seek out others’ presence (social affiliation) or avoid others’ presence (social isolation). The determinants and effects of social affiliation are now well-known, but social psychologists have not yet thoroughly studied social isolation. This study aims to ascertain which motives and corresponding regulation strategies participants report for social isolation following negative emotional events. A group of 96 participants retrieved from memory an actual negative event that led them to temporarily socially isolate themselves and freely listed up to 10 motives for social isolation. Through semantic categorization of the 423 motives reported by the participants, we found that “cognitive clarification” and “keeping one’s distance” – that is, the need for cognitive regulation and the refusal of socioaffective regulation, respectively – were the most commonly and quickly reported motives for social isolation. We discuss the findings in terms of ideas for future studies aimed at clarifying the role of social isolation in health situations.

scholarly journals The MarR-Type Regulator PA3458 Is Involved in Osmoadaptation Control in Pseudomonas aeruginosa

2021 ◽  
Vol 22 (8) ◽  
pp. 3982
Author(s):  
Karolina Kotecka ◽  
Adam Kawalek ◽  
Kamil Kobylecki ◽  
Aneta Agnieszka Bartosik
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Binding Sites ◽  
Transcriptional Profiling ◽  
Mrna Level ◽  
Transcriptional Regulators ◽  
Resistance Mechanisms ◽  
Chronic Infections ◽  
Environmental Signals ◽  
Regulatory Systems

Pseudomonas aeruginosa is a facultative human pathogen, causing acute and chronic infections that are especially dangerous for immunocompromised patients. The eradication of P. aeruginosa is difficult due to its intrinsic antibiotic resistance mechanisms, high adaptability, and genetic plasticity. The bacterium possesses multilevel regulatory systems engaging a huge repertoire of transcriptional regulators (TRs). Among these, the MarR family encompasses a number of proteins, mainly acting as repressors, which are involved in response to various environmental signals. In this work, we aimed to decipher the role of PA3458, a putative MarR-type TR from P. aeruginosa. Transcriptional profiling of P. aeruginosa PAO1161 overexpressing PA3458 showed changes in the mRNA level of 133 genes; among them, 100 were down-regulated, suggesting the repressor function of PA3458. Concomitantly, ChIP-seq analysis identified more than 300 PA3458 binding sites in P. aeruginosa. The PA3458 regulon encompasses genes involved in stress response, including the PA3459–PA3461 operon, which is divergent to PA3458. This operon encodes an asparagine synthase, a GNAT-family acetyltransferase, and a glutamyl aminopeptidase engaged in the production of N-acetylglutaminylglutamine amide (NAGGN), which is a potent bacterial osmoprotectant. We showed that PA3458-mediated control of PA3459–PA3461 expression is required for the adaptation of P. aeruginosa growth in high osmolarity. Overall, our data indicate that PA3458 plays a role in osmoadaptation control in P. aeruginosa.

scholarly journals The Role of Putative Fibrinogen Aα-, Bβ-, and γA-chain Integrin Binding Sites in Endothelial Cell-mediated Clot Retraction

1997 ◽  
Vol 272 (35) ◽  
pp. 22080-22085 ◽  
Author(s):  
Richard A. Smith ◽  
M. W. Mosesson ◽  
Michael M. Rooney ◽  
Susan T. Lord ◽  
A.U. Daniels ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Binding Sites ◽  
Clot Retraction
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