scholarly journals Dynamics of tRNA fragments and their targets in aging mammalian brain

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2758 ◽  
Author(s):  
Spyros Karaiskos ◽  
Andrey Grigoriev
Keyword(s):  
Small Rna ◽  
Mammalian Brain ◽  
Trna Genes ◽  
Ontology Term ◽  
Transcript Levels ◽  
Sequencing Technologies ◽  
Term Enrichment ◽  
Old Rats ◽  
Brain Target ◽  
Experimental Findings

Background: The progress of next-generation sequencing technologies has unveiled various non-coding RNAs that have previously been considered products of random degradation and attracted only minimal interest. Among small RNA families, microRNA (miRNAs) have traditionally been considered key post-transcriptional regulators. However, recent studies have reported evidence for widespread presence of fragments of tRNA molecules (tRFs) across a range of organisms and tissues, and of tRF involvement in Argonaute complexes. Methods:To elucidate potential tRF functionality, we compared available RNA sequencing datasets derived from the brains of young, mid-aged and old rats. Using sliding 7-mer windows along a tRF, we searched for putative seed sequences with high numbers of conserved complementary sites within 3' UTRs of 23 vertebrate genomes. We analyzed Gene Ontology term enrichment of predicted tRF targets and compared their transcript levels with targets of miRNAs in the context of age. Results and Discussion: We detected tRFs originating from 3’- and 5’-ends of tRNAs in rat brains at significant levels. These fragments showed dynamic changes: 3’ tRFs monotonously increased with age, while 5’ tRFs displayed less consistent patterns. Furthermore, 3’ tRFs showed a narrow size range compared to 5’ tRFs, suggesting a difference in their biogenesis mechanisms. Similar to our earlier results in Drosophila and compatible with other experimental findings, we found “seed” sequence locations on both ends of different tRFs. Putative targets of these fragments were found to be enriched in neuronal and developmental functions. Comparison of tRFs and miRNAs increasing in abundance with age revealed small, but distinct changes in brain target transcript levels for these two types of small RNA, with the higher proportion of tRF targets decreasing with age. We also illustrated the utility of tRF analysis for annotating tRNA genes in sequenced genomes.

Novel risk factors for craniofacial microsomia and assessment of their utility in clinic diagnosis

2021 ◽  
Author(s):  
Xiaopeng Xu ◽  
Bingqing Wang ◽  
Zhuoyuan Jiang ◽  
Qi Chen ◽  
Ke Mao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Environmental Risk ◽  
Neural Crest Cell ◽  
Polygenic Risk Score ◽  
Expression Change ◽  
Ontology Term ◽  
Environmental Threats ◽  
Craniofacial Microsomia ◽  
Hypoxic Environment ◽  
Term Enrichment

Abstract Craniofacial microsomia (CFM, OMIM%164 210) is one of the most common congenital facial abnormalities worldwide, but it’s genetic risk factors and environmental threats are poorly investigated, as well as their interaction, making the diagnosis and prenatal screening of CFM impossible. We perform a comprehensive association study on the largest CFM cohort of 6074 samples. We identify 15 significant (P < 5 × 10−8) associated genomic loci (including eight previously reported) and decipher 107 candidates based on multi-omics data. Gene Ontology term enrichment found that these candidates are mainly enriched in neural crest cell (NCC) development and hypoxic environment. Single-cell RNA-seq data of mouse embryo demonstrate that nine of them show dramatic expression change during early cranial NCC development whose dysplasia is involved in pathogeny of CFM. Furthermore, we construct a well-performed CFM risk-predicting model based on polygenic risk score (PRS) method and estimate seven environmental risk factors that interacting with PRS. Single-nucleotide polymorphism-based PRS is significantly associated with CFM [P = 7.22 × 10−58, odds ratio = 3.15, 95% confidence interval (CI) 2.74–3.63], and the top fifth percentile has a 6.8-fold CFM risk comparing with the 10th percentile. Father’s smoking increases CFM risk as evidenced by interaction parameter of −0.324 (95% CI −0.578 to −0.070, P = 0.011) with PRS. In conclusion, the newly identified risk loci will significantly improve our understandings of genetics contribution to CFM. The risk prediction model is promising for CFM prediction, and father’s smoking is a key environmental risk factor for CFM through interacting with genetic factors.

scholarly journals A Small RNA-Catalytic Argonaute Pathway Tunes Germline Transcript Levels to Ensure Embryonic Divisions

Cell ◽  
2016 ◽  
Vol 165 (2) ◽  
pp. 396-409 ◽  
Author(s):  
Adina Gerson-Gurwitz ◽  
Shaohe Wang ◽  
Shashank Sathe ◽  
Rebecca Green ◽  
Gene W. Yeo ◽  
...  
Keyword(s):  
Small Rna ◽  
Transcript Levels ◽  
Germline Transcript

Quantifying the ‘escapers’ among RNA species

2015 ◽  
Vol 43 (6) ◽  
pp. 1215-1220 ◽  
Author(s):  
Iolanda Ferro ◽  
Zoya Ignatova
Keyword(s):  
Deep Sequencing ◽  
Trna Genes ◽  
Cellular Processes ◽  
Functional Integrity ◽  
New Approaches ◽  
Sequencing Technologies ◽  
Specific Manner ◽  
Response To Stress ◽  
Identification And Quantification

tRNAs are fundamental components of translation and emerging evidence places them more centrally in various other cellular processes. However, rather than being uniformly conserved, tRNA abundance is instead highly variable and adaptable. The amount of tRNA genes greatly differs among species. Moreover, even within the same genome, tRNA abundance shapes the proteome in a tissue- and cell-specific manner and is dynamically regulated in response to stress. Here, we review approaches for identification and quantification of tRNAs and their functional integrity. We discuss the resolution of each method and highlight new approaches with cell-wide resolution based on deep-sequencing technologies.

scholarly journals Proteins in DNA methylation and their role in neural stem cell proliferation and differentiation

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiaqi Sun ◽  
Junzheng Yang ◽  
Xiaoli Miao ◽  
Horace H. Loh ◽  
Duanqing Pei ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Central Nervous System ◽  
Nervous System ◽  
Brain Plasticity ◽  
Dna Methyltransferases ◽  
Fine Tuning ◽  
Mammalian Brain ◽  
Main Body ◽  
Sequencing Technologies ◽  
Proliferation And Differentiation

Abstract Background Epigenetic modifications, namely non-coding RNAs, DNA methylation, and histone modifications such as methylation, phosphorylation, acetylation, ubiquitylation, and sumoylation play a significant role in brain development. DNA methyltransferases, methyl-CpG binding proteins, and ten-eleven translocation proteins facilitate the maintenance, interpretation, and removal of DNA methylation, respectively. Different forms of methylation, including 5-methylcytosine, 5-hydroxymethylcytosine, and other oxidized forms, have been detected by recently developed sequencing technologies. Emerging evidence suggests that the diversity of DNA methylation patterns in the brain plays a key role in fine-tuning and coordinating gene expression in the development, plasticity, and disorders of the mammalian central nervous system. Neural stem cells (NSCs), originating from the neuroepithelium, generate neurons and glial cells in the central nervous system and contribute to brain plasticity in the adult mammalian brain. Main body Here, we summarized recent research in proteins responsible for the establishment, maintenance, interpretation, and removal of DNA methylation and those involved in the regulation of the proliferation and differentiation of NSCs. In addition, we discussed the interactions of chemicals with epigenetic pathways to regulate NSCs as well as the connections between proteins involved in DNA methylation and human diseases. Conclusion Understanding the interplay between DNA methylation and NSCs in a broad biological context can facilitate the related studies and reduce potential misunderstanding.

scholarly journals Common cell type nomenclature for the mammalian brain

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jeremy A Miller ◽  
Nathan W Gouwens ◽  
Bosiljka Tasic ◽  
Forrest Collman ◽  
Cindy TJ van Velthoven ◽  
...  
Keyword(s):  
Cell Types ◽  
Data Driven ◽  
Mammalian Brain ◽  
Gene Transcript ◽  
Cell Type ◽  
Sequencing Technologies ◽  
Multiple Organs ◽  
Source Data ◽  
The Common ◽  
Common Cell

The advancement of single-cell RNA-sequencing technologies has led to an explosion of cell type definitions across multiple organs and organisms. While standards for data and metadata intake are arising, organization of cell types has largely been left to individual investigators, resulting in widely varying nomenclature and limited alignment between taxonomies. To facilitate cross-dataset comparison, the Allen Institute created the common cell type nomenclature (CCN) for matching and tracking cell types across studies that is qualitatively similar to gene transcript management across different genome builds. The CCN can be readily applied to new or established taxonomies and was applied herein to diverse cell type datasets derived from multiple quantifiable modalities. The CCN facilitates assigning accurate yet flexible cell type names in the mammalian cortex as a step toward community-wide efforts to organize multi-source, data-driven information related to cell type taxonomies from any organism.

D-Aspartate amends reproductive performance of aged roosters by changing gene expression and testicular histology

2018 ◽  
Vol 30 (7) ◽  
pp. 1038 ◽  
Author(s):  
Mahdi Ansari ◽  
Mahdi Zhandi ◽  
Hamid Kohram ◽  
Mojtaba Zaghari ◽  
Mostafa Sadeghi ◽  
...  
Keyword(s):  
Reproductive Performance ◽  
Regulatory Protein ◽  
Sperm Concentration ◽  
Membrane Integrity ◽  
The Other ◽  
Nuclear Antigen ◽  
Ionotropic Receptor ◽  
Transcript Levels ◽  
Testicular Histology ◽  
Experimental Findings

Male broiler breeders (n = 32) of 55 weeks of age were administered four different doses of capsulated d-aspartate (DA; 0, 100, 200 or 300 mg kg−1 day−1, p.o. (DA0, DA100, DA200 and DA300 respectively)) for 12 successive weeks to assess reproductive performance, blood testosterone, testicular histology and transcript levels of steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (P450scc), androgen receptor (AR), LH receptor (LHR), 3β-hydroxysteroid dehydrogenase (3BHSD), proliferating cell nuclear antigen (PCNA), glutamate ionotropic receptor NMDA type subunit 1 (GRIN1) and glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B). Blood samples and ejaculates were collected, and bodyweight was recorded weekly for 10 weeks. AI was performed weekly for the last 2 weeks to determine the number of sperm penetration holes in the perivitelline layer, fertility and hatchability. Testes histology and transcript levels were evaluated in the 12th week. Bodyweight, numbers of Leydig cells and blood vessels, testis index and levels of sperm abnormalities were not affected (P > 0.05) by the treatment. However, sperm total and forward motility, plasma membrane integrity and functionality of sperm, ejaculate volume, testosterone concentration and fertility were higher (P < 0.05) in both the DA200 and DA300 groups compared with the other groups. In the DA100 and DA200 groups, sperm concentration, number of spermatogonia, thickness of the seminiferous epithelium and the diameter of tubules were significantly higher (P < 0.05) than the other DA-treated groups. The number of penetration holes, hatchability and malondialdehyde concentration were higher in the DA200, all DA-treated and DA300 groups respectively compared with the control and other treatment groups. Except for P450scc, AR, LHR and PCNA transcript levels in the DA300 groups, the relative expression of the genes evaluated improved significantly in the other DA-treated groups. Based on these experimental findings, it is concluded that DA improves reproductive performance of aged roosters.

scholarly journals Transcriptome analysis of sevoflurane exposure effects at the different brain regions

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0236771
Author(s):  
Hiroto Yamamoto ◽  
Yutaro Uchida ◽  
Tomoki Chiba ◽  
Ryota Kurimoto ◽  
Takahide Matsushima ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Brain Regions ◽  
Rna Seq ◽  
Ontology Term ◽  
Binding Motifs ◽  
Term Enrichment Analysis ◽  
Term Enrichment ◽  
Differently Expressed Genes

Backgrounds Sevoflurane is a most frequently used volatile anesthetics, but its molecular mechanisms of action remain unclear. We hypothesized that specific genes play regulatory roles in brain exposed to sevoflurane. Thus, we aimed to evaluate the effects of sevoflurane inhalation and identify potential regulatory genes by RNA-seq analysis. Methods Eight-week old mice were exposed to sevoflurane. RNA from medial prefrontal cortex, striatum, hypothalamus, and hippocampus were analysed using RNA-seq. Differently expressed genes were extracted and their gene ontology terms were analysed using Metascape. These our anesthetized mouse data and the transcriptome array data of the cerebral cortex of sleeping mice were compared. Finally, the activities of transcription factors were evaluated using a weighted parametric gene set analysis (wPGSA). JASPAR was used to confirm the existence of binding motifs in the upstream sequences of the differently expressed genes. Results The gene ontology term enrichment analysis result suggests that sevoflurane inhalation upregulated angiogenesis and downregulated neural differentiation in each region of brain. The comparison with the brains of sleeping mice showed that the gene expression changes were specific to anesthetized mice. Focusing on individual genes, sevoflurane induced Klf4 upregulation in all sampled parts of brain. wPGSA supported the function of KLF4 as a transcription factor, and KLF4-binding motifs were present in many regulatory regions of the differentially expressed genes. Conclusions Klf4 was upregulated by sevoflurane inhalation in the mouse brain. The roles of KLF4 might be key to elucidating the mechanisms of sevoflurane induced functional modification in the brain.

scholarly journals Structural and Functional Aspects of the Neurodevelopmental Gene NR2F1: From Animal Models to Human Pathology

2021 ◽  
Vol 14 ◽  
Author(s):  
Chiara Tocco ◽  
Michele Bertacchi ◽  
Michèle Studer
Keyword(s):  
Thyroid Hormone Receptor ◽  
Clinical Signs ◽  
Autistic Traits ◽  
Network Activity ◽  
Mammalian Brain ◽  
Future Research ◽  
Cellular Models ◽  
Human Pathology ◽  
Developing Mouse Brain ◽  
Experimental Findings

The assembly and maturation of the mammalian brain result from an intricate cascade of highly coordinated developmental events, such as cell proliferation, migration, and differentiation. Any impairment of this delicate multi-factorial process can lead to complex neurodevelopmental diseases, sharing common pathogenic mechanisms and molecular pathways resulting in multiple clinical signs. A recently described monogenic neurodevelopmental syndrome named Bosch-Boonstra-Schaaf Optic Atrophy Syndrome (BBSOAS) is caused by NR2F1 haploinsufficiency. The NR2F1 gene, coding for a transcriptional regulator belonging to the steroid/thyroid hormone receptor superfamily, is known to play key roles in several brain developmental processes, from proliferation and differentiation of neural progenitors to migration and identity acquisition of neocortical neurons. In a clinical context, the disruption of these cellular processes could underlie the pathogenesis of several symptoms affecting BBSOAS patients, such as intellectual disability, visual impairment, epilepsy, and autistic traits. In this review, we will introduce NR2F1 protein structure, molecular functioning, and expression profile in the developing mouse brain. Then, we will focus on Nr2f1 several functions during cortical development, from neocortical area and cell-type specification to maturation of network activity, hippocampal development governing learning behaviors, assembly of the visual system, and finally establishment of cortico-spinal descending tracts regulating motor execution. Whenever possible, we will link experimental findings in animal or cellular models to corresponding features of the human pathology. Finally, we will highlight some of the unresolved questions on the diverse functions played by Nr2f1 during brain development, in order to propose future research directions. All in all, we believe that understanding BBSOAS mechanisms will contribute to further unveiling pathophysiological mechanisms shared by several neurodevelopmental disorders and eventually lead to effective treatments.

scholarly journals A role for noncanonical microRNAs in the mammalian brain revealed by phenotypic differences in Dgcr8 versus Dicer1 knockouts and small RNA sequencing

RNA ◽  
2011 ◽  
Vol 17 (8) ◽  
pp. 1489-1501 ◽  
Author(s):  
J. E. Babiarz ◽  
R. Hsu ◽  
C. Melton ◽  
M. Thomas ◽  
E. M. Ullian ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Small Rna ◽  
Mammalian Brain ◽  
Small Rna Sequencing ◽  
Phenotypic Differences

scholarly journals Methodologies for In Vitro Cloning of Small RNAs and Application for Plant Genome(s)

2009 ◽  
Vol 2009 ◽  
pp. 1-13 ◽  
Author(s):  
Eric J. Devor ◽  
Lingyan Huang ◽  
Abdusattor Abdukarimov ◽  
Ibrokhim Y. Abdurakhmonov
Keyword(s):  
Small Rna ◽  
High Throughput Sequencing ◽  
Rna World ◽  
Regulatory Elements ◽  
Plant Genome ◽  
Transcriptional Gene Silencing ◽  
Small Interfering Rnas ◽  
Sequencing Technologies ◽  
Post Transcriptional Gene Silencing

The “RNA revolution” that started at the end of the 20th century with the discovery of post-transcriptional gene silencing and its mechanism via RNA interference (RNAi) placed tiny 21-24 nucleotide long noncoding RNAs (ncRNAs) in the forefront of biology as one of the most important regulatory elements in a host of physiologic processes. The discovery of new classes of ncRNAs including endogenous small interfering RNAs, microRNAs, and PIWI-interacting RNAs is a hallmark in the understanding of RNA-dependent gene regulation. New generation high-throughput sequencing technologies further accelerated the studies of this “tiny world” and provided their global characterization and validation in many biological systems with sequenced genomes. Nevertheless, for the many “yet-unsequenced” plant genomes, the discovery of small RNA world requires in vitro cloning from purified cellular RNAs. Thus, reproducible methods for in vitro small RNA cloning are of paramount importance and will remain so into the foreseeable future. In this paper, we present a description of existing small RNA cloning methods as well as next-generation sequencing methods that have accelerated this research along with a description of the application of one in vitro cloning method in an initial small RNA survey in the “still unsequenced” allotetraploid cotton genome.

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