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1.
PLoS Biol ; 17(9): e3000396, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31532761

RESUMO

The canonical model of eukaryotic translation posits that efficient translation initiation increases protein expression and mRNA stability. Contrary to this model, we find that increasing initiation rate can decrease both protein expression and stability of certain mRNAs in the budding yeast Saccharomyces cerevisiae. These mRNAs encode a stretch of polybasic residues that cause ribosome stalling. Our computational modeling predicts that the observed decrease in gene expression at high initiation rates occurs when ribosome collisions at stalls stimulate abortive termination of the leading ribosome or cause endonucleolytic mRNA cleavage. Consistent with this prediction, the collision-associated quality-control factors Asc1 and Hel2 (orthologs of human RACK1 and ZNF598, respectively) decrease gene expression from stall-containing mRNAs only at high initiation rates. Remarkably, hundreds of S. cerevisiae mRNAs that contain ribosome stall sequences also exhibit lower translation efficiency. We propose that inefficient translation initiation allows these stall-containing endogenous mRNAs to escape collision-stimulated reduction in gene expression.


Assuntos
Iniciação Traducional da Cadeia Peptídica , RNA Mensageiro/fisiologia , Ribossomos/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteínas de Ligação ao GTP/fisiologia , Saccharomyces cerevisiae , Proteínas de Saccharomyces cerevisiae/fisiologia , Ubiquitina-Proteína Ligases/fisiologia
2.
PLoS Genet ; 15(9): e1008338, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31525188

RESUMO

Animal development requires the execution of specific transcriptional programs in different sets of cells to build tissues and functional organs. Transcripts are exported from the nucleus to the cytoplasm where they are translated into proteins that, ultimately, carry out the cellular functions. Here we show that in Caenorhabditis elegans, reduction of mRNA export strongly affects epithelial morphogenesis and germline proliferation while other tissues remain relatively unaffected. Epithelialization and gamete formation demand a large number of transcripts in the cytoplasm for the duration of these processes. In addition, our findings highlight the existence of a regulatory feedback mechanism that activates gene expression in response to low levels of cytoplasmic mRNA. We expand the genetic characterization of nuclear export factor NXF-1 to other members of the mRNA export pathway to model mRNA export and recycling of NXF-1 back to the nucleus. Our model explains how mutations in genes involved in general processes, such as mRNA export, may result in tissue-specific developmental phenotypes.


Assuntos
Especificidade de Órgãos/genética , Transporte de RNA/fisiologia , RNA Mensageiro/fisiologia , Transporte Ativo do Núcleo Celular/genética , Sequência de Aminoácidos , Animais , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Núcleo Celular/genética , Citoplasma/metabolismo , Proteínas de Transporte Nucleocitoplasmático/genética , Transporte de RNA/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética
3.
BMC Genomics ; 20(1): 512, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221080

RESUMO

BACKGROUND: Dermal papilla cells (DPCs), the "signaling center" of hair follicle (HF), delicately master continual growth of hair in mammals including cashmere, the fine fiber annually produced by secondary HF embedded in cashmere goat skins. Such unparalleled capacity bases on their exquisite character in instructing the cellular activity of hair-forming keratinocytes via secreting numerous molecular signals. Past studies suggested microRNA (miRNAs) and long non-coding RNAs (lncRNAs) play essential roles in a wide variety of biological process, including HF cycling. However, their roles and related molecular mechanisms in modulating DPCs secretory activities are still poorly understood. RESULTS: Here, we separately cultivated DPCs and their functionally and morphologically distinct dermal fibroblasts (DFs) from cashmere goat skins at anagen. With the advantage of high throughput RNA-seq, we synchronously identified 2540 lncRNAs and 536 miRNAs from two types of cellular samples at 4th passages. Compared with DFs, 1286 mRNAs, 18 lncRNAs, and 42 miRNAs were upregulated, while 1254 mRNAs, 53 lncRNAs and 44 miRNAs were downregulated in DPCs. Through overlapping with mice data, we ultimately defined 25 core signatures of DPCs, including HOXC8 and RSPO1, two crucial activators for hair follicle stem cells (HFSCs). Subsequently, we emphatically investigated the impacts of miRNAs and lncRNAs (cis- and trans- acting) on the genes, indicating that ncRNAs extensively exert negative and positive effects on their expressions. Furthermore, we screened lncRNAs acting as competing endogenous RNAs (ceRNAs) to sponge miRNAs and relief their repressive effects on targeted genes, and constructed related lncRNAs-miRNAs-HOXC8/RSPO1 interactive lines using bioinformatic tools. As a result, XR_310320.3-chi-miR-144-5p-HOXC8, XR_311077.2-novel_624-RSPO1 and others lines appeared, displaying that lncRNAs might serve as ceRNAs to indirectly adjust HFSCs status in hair growth. CONCLUSION: The present study provides an unprecedented inventory of lncRNAs, miRNAs and mRNAs in goat DPCs and DFs. We also exhibit some miRNAs and lncRNAs potentially participate in the modulation of HFSCs activation via delicately adjusting core signatures of DPCs. Our report shines new light on the latent roles and underlying molecular mechanisms of ncRNAs on hair growth.


Assuntos
Cabras/genética , Folículo Piloso/metabolismo , RNA Mensageiro/fisiologia , RNA não Traduzido/fisiologia , Animais , Derme/citologia , Feminino , Fibroblastos/metabolismo , Cabras/metabolismo , Cabelo/crescimento & desenvolvimento , Proteínas de Homeodomínio/genética , Humanos , Camundongos , MicroRNAs/metabolismo , Pele/citologia , Trombospondinas/genética , Transcriptoma
4.
Folia Histochem Cytobiol ; 57(2): 64-73, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31246264

RESUMO

INTRODUCTION: This study endeavors to analyze the effects of miR-1204 on the expression of DEK oncogene in non-small cell lung cancer (NSCLC) cell lines and to study the molecular mechanisms of these effects. MATERIAL AND METHODS: The miR-1204 mimics and inhibitors were transfected into the (A549 and SPC) NSCLC cells. Then the mRNA levels, cell viability, apoptosis rate, morphology and caspase activity were determined. The expression of apoptosis-related proteins Bcl-2 and Bax was also analyzed. RESULTS: In NSCLC cell lines (A549 and SPC), DEK mRNA levels were down-regulated in miR-1204 overex-pression group. In miR-1204 inhibition group, the expression of DEK mRNA showed an opposite trend. The overexpression of miR-1204 increases the apoptosis rate in NSCLC cells. The Bcl-2 levels in the miR-1204 over-expression group were decreased, while the Bax level was increased. In the miR-1204 inhibition group, expression of Bcl-2 and Bax showed opposite trends. Cell staining revealed cell's morphological changes; the apoptosis in the miR-1204 overexpression group revealed significant morphological features, such as brighter nuclei and nu-clear condensation. Results indicated a typical characteristic of apoptosis in the miR-1204 overexpression group. Caspase-9 and Caspase-3 were involved in the apoptosis pathway, which was mediated by miR-1204 and DEK. CONCLUSIONS: The miR-1204 induces apoptosis of NSCLC cells by inhibiting the expression of DEK. The mech-anism of apoptosis involves down-regulation of Bcl-2 and up-regulation of Bax expression. Moreover, the apoptosis was mediated by mitochondria-related caspase 9/3 pathway.


Assuntos
Apoptose/fisiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas Cromossômicas não Histona/genética , Neoplasias Pulmonares/genética , MicroRNAs/fisiologia , Proteínas Oncogênicas/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , RNA Mensageiro/fisiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Regulação para Cima , Proteína X Associada a bcl-2/metabolismo
5.
Cell ; 176(1-2): 56-72.e15, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30612743

RESUMO

Local translation regulates the axonal proteome, playing an important role in neuronal wiring and axon maintenance. How axonal mRNAs are localized to specific subcellular sites for translation, however, is not understood. Here we report that RNA granules associate with endosomes along the axons of retinal ganglion cells. RNA-bearing Rab7a late endosomes also associate with ribosomes, and real-time translation imaging reveals that they are sites of local protein synthesis. We show that RNA-bearing late endosomes often pause on mitochondria and that mRNAs encoding proteins for mitochondrial function are translated on Rab7a endosomes. Disruption of Rab7a function with Rab7a mutants, including those associated with Charcot-Marie-Tooth type 2B neuropathy, markedly decreases axonal protein synthesis, impairs mitochondrial function, and compromises axonal viability. Our findings thus reveal that late endosomes interact with RNA granules, translation machinery, and mitochondria and suggest that they serve as sites for regulating the supply of nascent pro-survival proteins in axons.


Assuntos
Endossomos/fisiologia , Biossíntese de Proteínas/fisiologia , Proteínas rab de Ligação ao GTP/metabolismo , Animais , Axônios/metabolismo , Endossomos/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , RNA/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/fisiologia , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/fisiologia , Ribossomos/metabolismo , Proteínas de Xenopus/metabolismo , Xenopus laevis/metabolismo , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/fisiologia
6.
J Vis Exp ; (141)2018 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-30531717

RESUMO

Induced pluripotent stem cells (iPSCs) have proven to be a valuable tool to study human development and disease. Further advancing iPSCs as a regenerative therapeutic requires a safe, robust, and expedient reprogramming protocol. Here, we present a clinically relevant, step-by-step protocol for the extremely high-efficiency reprogramming of human dermal fibroblasts into iPSCs using a non-integrating approach. The core of the protocol consists of expressing pluripotency factors (SOX2, KLF4, cMYC, LIN28A, NANOG, OCT4-MyoD fusion) from in vitro transcribed messenger RNAs synthesized with modified nucleotides (modified mRNAs). The reprogramming modified mRNAs are transfected into primary fibroblasts every 48 h together with mature embryonic stem cell-specific microRNA-367/302 mimics for two weeks. The resulting iPSC colonies can then be isolated and directly expanded in feeder-free conditions. To maximize efficiency and consistency of our reprogramming protocol across fibroblast samples, we have optimized various parameters including the RNA transfection regimen, timing of transfections, culture conditions, and seeding densities. Importantly, our method generates high-quality iPSCs from most fibroblast sources, including difficult-to-reprogram diseased, aged, and/or senescent samples.


Assuntos
Reprogramação Celular/fisiologia , Fibroblastos/fisiologia , Células-Tronco Pluripotentes Induzidas/fisiologia , MicroRNAs/fisiologia , RNA Mensageiro/fisiologia , Diferenciação Celular/fisiologia , Células Cultivadas , Engenharia Genética/métodos , Humanos , Transfecção/métodos
7.
J Am Heart Assoc ; 7(20): e010378, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30371266

RESUMO

Background The molecular mechanisms mediating postnatal loss of cardiac regeneration in mammals are not fully understood. We aimed to provide an integrated resource of mRNA , protein, and metabolite changes in the neonatal heart for identification of metabolism-related mechanisms associated with cardiac regeneration. Methods and Results Mouse ventricular tissue samples taken on postnatal day 1 (P01), P04, P09, and P23 were analyzed with RNA sequencing and global proteomics and metabolomics. Gene ontology analysis, KEGG pathway analysis, and fuzzy c-means clustering were used to identify up- or downregulated biological processes and metabolic pathways on all 3 levels, and Ingenuity pathway analysis (Qiagen) was used to identify upstream regulators. Differential expression was observed for 8547 mRNA s and for 1199 of 2285 quantified proteins. Furthermore, 151 metabolites with significant changes were identified. Differentially regulated metabolic pathways include branched chain amino acid degradation (upregulated at P23), fatty acid metabolism (upregulated at P04 and P09; downregulated at P23) as well as the HMGCS ( HMG -CoA [hydroxymethylglutaryl-coenzyme A] synthase)-mediated mevalonate pathway and ketogenesis (transiently activated). Pharmacological inhibition of HMGCS in primary neonatal cardiomyocytes reduced the percentage of BrdU-positive cardiomyocytes, providing evidence that the mevalonate and ketogenesis routes may participate in regulating the cardiomyocyte cell cycle. Conclusions This study is the first systems-level resource combining data from genomewide transcriptomics with global quantitative proteomics and untargeted metabolomics analyses in the mouse heart throughout the early postnatal period. These integrated data of molecular changes associated with the loss of cardiac regeneration may open up new possibilities for the development of regenerative therapies.


Assuntos
Coração/crescimento & desenvolvimento , Camundongos/crescimento & desenvolvimento , Aminoácidos de Cadeia Ramificada/metabolismo , Animais , Animais Recém-Nascidos/crescimento & desenvolvimento , Ácidos Graxos/metabolismo , Expressão Gênica/fisiologia , Coração/embriologia , Ventrículos do Coração , Corpos Cetônicos/biossíntese , Metabolômica , Ácido Mevalônico/metabolismo , Proteômica , RNA Mensageiro/genética , RNA Mensageiro/fisiologia , Transcriptoma/fisiologia
9.
Virology ; 525: 96-105, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30253276

RESUMO

Cellular mRNAs cycle between translating and non-translating pools, polysomes compose the translating pool, while RNA granules contain translationally-silenced mRNAs, where the RNAs are either stored in stress granules, or accumulate in processing bodies (PBs) or GW-bodies, which have an important role in RNA degradation. Viruses have developed measures to prevent the deleterious effects of these structures during their replication. Rotavirus, the most common agent of viral gastroenteritis, is capable of establishing a successful infection by counteracting several of the antiviral responses of its host. Here, we describe that in rotavirus-infected cells the distribution of several RNA binding proteins is changed causing the disaggregation of PBs, the relocalization of GW-body proteins, and the cytoplasmic accumulation of HuR, a predominantly nuclear protein. We show that this redistribution of proteins is more likely caused by the accumulation of viral RNA in the cytoplasm of infected-cells, where it might be acting as an RBP sponge.


Assuntos
Transporte Proteico/fisiologia , RNA Viral/fisiologia , Proteínas de Ligação a RNA/fisiologia , Rotavirus/genética , Animais , Anticorpos Antivirais , Linhagem Celular , Regulação da Expressão Gênica , Macaca mulatta , RNA Mensageiro/química , RNA Mensageiro/fisiologia , Proteínas de Ligação a RNA/química , Rotavirus/fisiologia
10.
Aging (Albany NY) ; 10(9): 2266-2283, 2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30187887

RESUMO

Atherosclerosis is a chronic and multifactorial inflammatory disease and is closely associated with cardiovascular and cerebrovascular diseases. circRNAs can act as competing endogenous RNAs to mRNAs and function in various diseases. However, there is little known about the function of circRNAs in atherosclerosis. In this study, three rabbits in the case group were fed a high-fat diet to induce atherosclerosis and another three rabbits were fed a normal diet. To explore the biological functions of circRNAs in atherosclerosis, we analyzed the circRNA, miRNA and mRNA expression profiles using RNA-seq. Many miRNAs, mRNAs and circRNAs were identified as significantly changed in atherosclerosis. We next predicted miRNA-target interactions with the miRanda tool and constructed a differentially expressed circRNA-miRNA-mRNA triple network. A gene ontology enrichment analysis showed that genes in the network were involved in cell adhesion, cell activation and the immune response. Furthermore, we generated a dysregulated circRNA-related ceRNAs network and found seven circRNAs (ocu-cirR-novel-18038, -18298, -15993, -17934, -17879, -18036 and -14389) were related to atherosclerosis. We found these circRNAs also functioned in cell adhesion, cell activation and the immune response. These results show that the crosstalk between circRNAs and their competing mRNAs might play crucial roles in the development of atherosclerosis.


Assuntos
Aterosclerose/etiologia , MicroRNAs/fisiologia , RNA Mensageiro/fisiologia , RNA/fisiologia , Animais , Aterosclerose/genética , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Ontologia Genética , MicroRNAs/análise , RNA/análise , RNA Mensageiro/análise , Coelhos , Análise de Sequência de RNA
11.
Mol Genet Genomics ; 293(6): 1535-1546, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30116946

RESUMO

Polyploidization is considered as the major force that drives plant species evolution and biodiversity. The leaves of Chinese cabbage, an important vegetable crop valued for its nutritional quality, constitute the main edible organ. In this study, we found that autotetraploid Chinese cabbage (Brassica rapa ssp. pekinensis) generated from a doubled haploid (DH) line via isolated microspore culture exhibits a dwarf phenotype, along with thick leaves and delayed flowering. Abscisic acid (ABA) and brassinosteroid (BR) levels were significantly lower in autotetraploids compared to DHs. Comparative transcriptome analysis was performed to examine the gene regulatory network. A total of 13,225 differentially expressed genes (DEGs) were detected. Further microRNA (miRNA) analysis identified 102 DEGs that correspond to 35 differentially expressed miRNAs (DEMs). Subsequent screening of these 102 genes identified 13 key genes with 12 corresponding differentially expressed miRNAs that are related to leaf development and dwarfism. These 13 genes are involved in the regulation of various processes, including BR synthesis (dwarfing), plant growth, flowering time delay, ABA pathway-related growth and metabolism, leaf morphology and development, and cell extension. Two dwarfing-related genes (BraA01000252 and BraA05004386) regulated by two miRNAs (novel_15 and novel_54) were determined to be downregulated, indicating their possible role in leaf thickness and dwarfism in autotetraploid plants. We also propose two possible miRNA-dependent regulatory pathways that contribute to trait formation in autotetraploid Chinese cabbage. These results provide a theoretical basis for further work involving Chinese cabbage varieties by inducing polyploidy.


Assuntos
Brassica rapa/crescimento & desenvolvimento , Brassica rapa/genética , Redes Reguladoras de Genes/fisiologia , MicroRNAs/fisiologia , Reguladores de Crescimento de Planta/genética , RNA Mensageiro/fisiologia , Brassica rapa/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/fisiologia , Genes de Plantas , MicroRNAs/genética , Desenvolvimento Vegetal/genética , Reguladores de Crescimento de Planta/metabolismo , Reguladores de Crescimento de Planta/farmacologia , RNA Mensageiro/genética , Tetraploidia
12.
Braz J Med Biol Res ; 51(10): e7113, 2018 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-30066726

RESUMO

Dorsal root ganglia (DRG) neurons regenerate spontaneously after traumatic or surgical injury. Long noncoding RNAs (lncRNAs) are involved in various biological regulation processes. Conditions of lncRNAs in DRG neuron injury deserve to be further investigated. Transcriptomic analysis was performed by high-throughput Illumina HiSeq2500 sequencing to profile the differential genes in L4-L6 DRGs following rat sciatic nerve tying. A total of 1,228 genes were up-regulated and 1,415 down-regulated. By comparing to rat lncRNA database, 86 known and 26 novel lncRNA genes were found to be differential. The 86 known lncRNA genes modulated 866 target genes subject to gene ontology (GO) and KEGG enrichment analysis. The genes involved in the neurotransmitter status of neurons were downregulated and those involved in a neuronal regeneration were upregulated. Known lncRNA gene rno-Cntnap2 was downregulated. There were 13 credible GO terms for the rno-Cntnap2 gene, which had a putative function in cell component of voltage-gated potassium channel complex on the cell surface for neurites. In 26 novel lncRNA genes, 4 were related to 21 mRNA genes. A novel lncRNA gene AC111653.1 improved rno-Hypm synthesizing huntingtin during sciatic nerve regeneration. Real time qPCR results attested the down-regulation of rno-Cntnap lncRNA gene and the upregulation of AC111653.1 lncRNA gene. A total of 26 novel lncRNAs were found. Known lncRNA gene rno-Cntnap2 and novel lncRNA AC111653.1 were involved in neuropathic pain of DRGs after spared sciatic nerve injury. They contributed to peripheral nerve regeneration via the putative mechanisms.


Assuntos
Gânglios Espinais/lesões , Neuralgia/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , Nervo Isquiático/metabolismo , Transcriptoma , Animais , Sequência de Bases , Western Blotting , Mapeamento Cromossômico , Modelos Animais de Doenças , Gânglios Espinais/metabolismo , Gânglios Espinais/fisiopatologia , Regulação da Expressão Gênica , Masculino , Dados de Sequência Molecular , Neuralgia/genética , Neuralgia/fisiopatologia , Traumatismos dos Nervos Periféricos/genética , Traumatismos dos Nervos Periféricos/fisiopatologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , RNA Mensageiro/metabolismo , RNA Mensageiro/fisiologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Nervo Isquiático/fisiopatologia
13.
Am J Med Genet B Neuropsychiatr Genet ; 177(6): 563-579, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30105773

RESUMO

Major depression in negative mood is presumably induced by chronic stress with lack of reward. However, most individuals who experience chronic stress demonstrate resilience. Molecular mechanisms underlying stress- induced depression versus resilience remain unknown, which are investigated in brain reward circuits. Mice were treated by chronic unpredictable mild stress (CUMS) for 4 weeks. The tests of sucrose preference, Y-maze, and forced swimming were used to identify depression-like emotion behavior or resilience. High-throughput sequencing was used to analyze mRNA and miRNA quantity in the nucleus accumbens (NAc) harvested from the mice in the groups of control, CUMS-induced depression (CUMS-MDD), and CUMS-resistance to identify molecular profiles of CUMS-MDD versus CUMS-resilience. In data analyses and comparison among three groups, 1.5-fold ratio in reads per kilo-base per million reads (RPKM) was set to judge involvements of mRNA and miRNA in CUMS, MDD, or resilience. The downregulations of serotonergic/dopaminergic synapses, MAPK/calcium signaling pathways, and morphine addiction as well as the upregulations of cAMP/PI3K-Akt signaling pathways and amino acid metabolism are associated with CUMS-MDD. The downregulations of chemokine signaling pathway, synaptic vesicle cycle, and nicotine addiction as well as the upregulations of calcium signaling pathway and tyrosine metabolism are associated with CUMS-resilience. The impairments of serotonergic/dopaminergic synapses and PI3K-Akt/MAPK signaling pathways in the NAc are associated with depression. The upregulation of these entities is associated with resilience. Consistent results from analyzing mRNA/miRNA and using different methods validate our finding and conclusion.


Assuntos
Adaptação Psicológica/fisiologia , Depressão/etiologia , Depressão/genética , Animais , Depressão/fisiopatologia , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/genética , Modelos Animais de Doenças , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/fisiologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Núcleo Accumbens/metabolismo , Núcleo Accumbens/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/fisiologia , Resiliência Psicológica , Transdução de Sinais , Estresse Psicológico/complicações
14.
Microbiol Spectr ; 6(4)2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30006995

RESUMO

Previously, leaderless mRNAs (lmRNAs) were perceived to make up only a minor fraction of the transcriptome in bacteria. However, advancements in RNA sequencing technology are uncovering vast numbers of lmRNAs, particularly in archaea, Actinobacteria, and extremophiles and thus underline their significance in cellular physiology and regulation. Due to the absence of conventional ribosome binding signals, lmRNA translation initiation is distinct from canonical mRNAs and can therefore be differentially regulated. The ribosome's inherent ability to bind a 5'-terminal AUG can stabilize and protect the lmRNA from degradation or allow ribosomal loading for downstream initiation events. As a result, lmRNAs remain translationally competent during a variety of physiological conditions, allowing them to contribute to multiple regulatory mechanisms. Furthermore, the abundance of lmRNAs can increase during adverse conditions through the upregulation of lmRNA transcription from alternative promoters or by the generation of lmRNAs from canonical mRNAs cleaved by an endonucleolytic toxin. In these ways, lmRNA translation can continue during stress and contribute to regulation, illustrating their importance in the cell. Due to their presence in all domains of life and their ability to be translated by heterologous hosts, lmRNAs appear further to represent ancestral transcripts that might allow us to study the evolution of the ribosome and the translational process.


Assuntos
Archaea/metabolismo , Bactérias/metabolismo , RNA Bacteriano/fisiologia , RNA Mensageiro/fisiologia , Regiões 5' não Traduzidas , Archaea/genética , Bactérias/genética , Sequência de Bases , Códon de Iniciação , Regulação da Expressão Gênica em Archaea/fisiologia , Regulação Bacteriana da Expressão Gênica/fisiologia , Proteínas Ribossômicas , Estresse Psicológico , Transcriptoma
15.
BMC Plant Biol ; 18(1): 75, 2018 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-29728060

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in multiple biological processes in both mammals and plants. There is growing evidence that they are associated with development; but their expression and regulation during fruit ripening in the model plant tomato (Solanum lycopersicum) has yet to be described. RESULTS: Following integration of 134 RNA-seq data sets, we identified 79,322 putative lncRNAs, consisting of 70,635 lincRNAs, 8085 antisense non-coding RNAs (ancRNAs) and 602 sense lncRNAs (slncRNAs). lncRNAs had specific features that are distinct from mRNAs, including tissue-specificity, and shorter and fewer exons. Notably, more than 5000 of the novel lincRNAs were found to be expressed across the mature green (MG), breaker (BR) and breaker plus 7 days (BR + 7) developmental stages. The differently expressed lincRNAs had different DNA methylation profiles from the mRNAs. CONCLUSIONS: Integrating transcriptome datasets and genome-wide screening enabled the identification of a comprehensive set of tomato lncRNAs. Here, we found that the lncRNAs DNA methylation profiles were different from those of mRNAs. This will help future investigation of lncRNA function, especially for the dissection of the molecular mechanisms involved in the regulation of fruit development.


Assuntos
Frutas/genética , Genoma de Planta/genética , Lycopersicon esculentum/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Metilação de DNA , Frutas/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Genoma de Planta/fisiologia , Lycopersicon esculentum/crescimento & desenvolvimento , RNA Longo não Codificante/fisiologia , RNA Mensageiro/fisiologia , Transcriptoma
16.
Epigenomics ; 10(5): 661-671, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29692219

RESUMO

Protein coding sequences account for around 3% of the human genome, the rest are noncoding RNA (ncRNA) including long ncRNA (lncRNA) and miRNA. Accumulating evidence indicates that lncRNAs and miRNAs are candidate biomarkers for diagnosis, prognosis and therapy of cardiovascular diseases. The lncRNAs act as sponge-like effects on numerous miRNAs, subsequently regulating miRNAs and their targets, mRNA functions. The role of lncRNA-miRNA-mRNA axis in pathogenesis of cardiovascular diseases has been recently reported and highlighted. Herein, this review discusses emerging roles of lncRNA-miRNA-mRNA axis in cardiovascular pathophysiology and regulation, with a novel focus on cardioprotective network activities of the two subgroup ncRNAs.


Assuntos
Doenças Cardiovasculares/genética , Doenças Cardiovasculares/terapia , MicroRNAs/fisiologia , RNA Longo não Codificante/fisiologia , RNA Mensageiro/fisiologia , Biomarcadores/metabolismo , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , Prognóstico , RNA Longo não Codificante/genética , RNA Mensageiro/genética
17.
J Exp Zool B Mol Dev Evol ; 330(3): 181-187, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29682883

RESUMO

In oocytes, RNA localization has critical implications, as assembly of proteins in particular subcellular domains is crucial to embryo development. The distribution of mRNA molecules can identify and characterize localized transcripts. The goal of this study was to clarify the origin of primordial germ cells in the oocyte body plan and to reveal the generation of cell lineages by localized RNAs. The distribution of 12 selected mRNAs in sterlet Acipenser ruthenus oocytes was investigated by qPCR tomography and compared with known patterns of mRNA localization in Xenopus laevis. We investigated the distribution of two gene clusters in the ooplasm along the animal-vegetal axis of the sturgeon oocyte, both of which showed clearly defined intracellular gradient pattern remarkably similar to their distribution in the frog oocyte. We elucidated the localization of sturgeon egg germplasm markers belonging to the vegetal group of mRNAs. The mRNAs coding otx1, wnt11, and veg1 found to be localized in the sturgeon animal hemisphere are, in contrast, distributed in the vegetal hemisphere in amphibian. Actinopterygii and Sarcopterygii, two major lineages of osteichthyan vertebrates, split about 476 Ma (Blair & Hedges, ), albeit basal lineages share conserved biological features. Acipenseriformes is one the most basal living lineages of Actinopterygii, having evolved about 200 Ma (Bemis, Birstein, & Waldman, ), contemporaneous with modern amphibians (Roelants et al., ).


Assuntos
Peixes , Oócitos/fisiologia , Transporte Proteico/fisiologia , RNA Mensageiro/fisiologia , Xenopus , Animais , Evolução Biológica , Especificidade da Espécie
18.
J Toxicol Sci ; 43(4): 281-289, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29618717

RESUMO

Our aim was to demonstrate the significance of miRNA, lncRNA, and circRNA in the transformation of human bronchial epithelial cells induced by benzo(a)pyrene (BaP), and to investigate their regulatory networks. Hierarchical clustering, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and network regulation analysis were used to analyze the high-throughput sequencing results of human bronchial epithelial cell line BEAS-2B and BaP-transformed BEAS-2B cells (BEAS-2B-T). 76,191,786 and 3,431differentially-expressed miRNA, lncRNA, mRNA and circRNA were detected, respectively; 43 miRNA, 48 lncRNA, 438 mRNA and 2,079 circRNA were up-regulated; 33 miRNA, 143 lncRNA, 348 mRNA and 1,352 circRNA were down-regulated. Through GO analysis, 257 biological process (BP) terms, 12 cell composition (CC) terms and 49 molecular function (MF) terms were found in differentially-expressed lncRNA; 143 BP terms, 32 CC terms, and 48 MF terms were found in differentially-expressed circRNA. Pathways of KEGG analysis of lncRNA and circRNA could be classified into the categories "human diseases" and "organism systems". From miRNA-circRNA, circRNA-mRNA, and lncRNA-circRNA networks analysis, we found that mir-137, circ-RPS5, circ-ZNF292, circ-ERBB2IP, circ-SEMA3C, circ-IGF1R, circ-RTN4, APOC1, and CDKN2A may be of great significance for cell transformation. From the analysis of miRNA, lncRNA, mRNA, and circRNA networks, we found that PDGFRB, lncRNA RGMB-AS1, circ-ZNF292 are associated with miR-138-5p. Our study shows that miRNA, lncRNA, and circRNA have a significant regulatory role in the transformation of human bronchial epithelial cell induced by BaP.


Assuntos
Benzo(a)pireno/toxicidade , Brônquios/citologia , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/genética , Células Epiteliais/efeitos dos fármacos , MicroRNAs/fisiologia , RNA Mensageiro/fisiologia , Células Cultivadas , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos
19.
Brain Res ; 1693(Pt A): 24-36, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-29653083

RESUMO

Research in the past decades has unfolded the multifaceted role of Fragile X mental retardation protein (FMRP) and how its absence contributes to the pathophysiology of Fragile X syndrome (FXS). Excess signaling through group 1 metabotropic glutamate receptors is commonly observed in mouse models of FXS, which in part is attributed to dysregulated translation and downstream signaling. Considering the wide spectrum of cellular and physiologic functions that loss of FMRP can affect in general, it may be advantageous to pursue disease mechanism based treatments that directly target translational components or signaling factors that regulate protein synthesis. Various FMRP targets upstream and downstream of the translational machinery are therefore being investigated to further our understanding of the molecular mechanism of RNA and protein synthesis dysregulation in FXS as well as test their potential role as therapeutic interventions to alleviate FXS associated symptoms. In this review, we will broadly discuss recent advancements made towards understanding the role of FMRP in translation regulation, new pre-clinical animal models with FMRP targets located at different levels of the translational and signal transduction pathways for therapeutic intervention as well as future use of stem cells to model FXS associated phenotypes.


Assuntos
Proteína do X Frágil de Retardo Mental/genética , Proteína do X Frágil de Retardo Mental/fisiologia , Síndrome do Cromossomo X Frágil/genética , Animais , Dendritos/metabolismo , Modelos Animais de Doenças , Síndrome do Cromossomo X Frágil/fisiopatologia , Regulação da Expressão Gênica , Humanos , Biossíntese de Proteínas/genética , Biossíntese de Proteínas/fisiologia , RNA Mensageiro/metabolismo , RNA Mensageiro/fisiologia , Receptores de Glutamato Metabotrópico/fisiologia , Transdução de Sinais
20.
Hist Philos Life Sci ; 40(2): 25, 2018 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-29560537

RESUMO

Scientific hypotheses may either predict particular unknown facts or accommodate previously-known data. Although affirmed predictions are intuitively more rewarding than accommodations of established facts, opinions divide whether predictive hypotheses are also epistemically superior to accommodation hypotheses. This paper examines the contribution of predictive hypotheses to discoveries of several bio-molecular systems. Having all the necessary elements of the system known beforehand, an abstract predictive hypothesis of semiconservative mode of DNA replication was successfully affirmed. However, in defining the genetic code whose biochemical basis was unclear, hypotheses were only partially effective and supplementary experimentation was required for its conclusive definition. Markedly, hypotheses were entirely inept in predicting workings of complex systems that included unknown elements. Thus, hypotheses did not predict the existence and function of mRNA, the multiple unidentified components of the protein biosynthesis machinery, or the manifold unknown constituents of the ubiquitin-proteasome system of protein breakdown. Consequently, because of their inability to envision unknown entities, predictive hypotheses did not contribute to the elucidation of cation theories remained the sole instrument to explain complex bio-molecular systems, the philosophical question of alleged advantage of predictive over accommodative hypotheses became inconsequential.


Assuntos
Complexo de Endopeptidases do Proteassoma/fisiologia , Biossíntese de Proteínas/fisiologia , RNA Mensageiro/fisiologia , Ubiquitinas/fisiologia , Modelos Biológicos , Proteólise
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