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1.
Cell Mol Life Sci ; 76(21): 4203-4219, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31300868

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with a high mortality rate. Its dismal prognosis is attributed to late diagnosis, high risk of recurrence and drug resistance. To improve the survival of patients with HCC, new approaches are required for early diagnosis, real-time monitoring and effective treatment. Exosomes are small membranous vesicles released by most cells that contain biological molecules and play a great role in intercellular communication under physiological or pathological conditions. In cancer, exosomes from tumor cells or non-tumor cells can be taken up by neighboring or distant target cells, and the cargoes in exosomes are functional to modulate the behaviors of tumors or reshape tumor microenvironment (TME). As essential components, non-coding RNAs (ncRNAs) are selectively enriched in exosomes, and exosomal ncRNAs participate in regulating specific aspects of tumor development, including tumorigenesis, tumor metastasis, angiogenesis, immunomodulation and drug resistance. Besides, dysregulated exosomal ncRNAs have emerged as potential biomarkers, and exosomes can serve as natural vehicles to deliver tumor-suppressed ncRNAs for treatment. In this review, we briefly summarize the biology of exosomes, the functions of exosomal ncRNAs in HCC development and their potential clinical applications, including as biomarkers and therapeutic tools.


Assuntos
Carcinoma Hepatocelular/genética , Exossomos/genética , Neoplasias Hepáticas/genética , RNA Neoplásico/fisiologia , RNA não Traduzido/fisiologia , Animais , Biomarcadores Tumorais/fisiologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Sistemas de Liberação de Medicamentos , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Terapia Genética/métodos , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Terapia de Alvo Molecular/métodos , RNA Neoplásico/metabolismo , RNA não Traduzido/metabolismo
2.
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
3.
Nat Protoc ; 14(5): 1489-1508, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30962605

RESUMO

Non-coding RNA (ncRNA) molecules have been shown to play a variety of cellular roles; however, the contributions of different types of RNA to specific phenomena are often hard to dissect. To study the role of RNA in the assembly of DNA damage response (DDR) foci, we developed the RNase A treatment and reconstitution (RATaR) method, in which cells are mildly permeabilized, incubated with recombinant RNase A and subsequently reconstituted with different RNA species, under conditions of RNase A inactivation and inhibition of endogenous transcription. The block of transcription right after RNase A removal represents a key innovation of RATaR, preventing potential contributions of endogenously neo-synthesized transcripts to the phenotypes studied. A critical aspect of this technique is the balance between sufficient permeabilization of membranes to allow enzyme/RNA access into the cell nucleus and cell viability. Here, we present our protocol for RNA-dependent DDR foci disassembly and reassembly using fluorescent DDR RNAs (DDRNAs) in NIH2/4 cells, an engineered NIH3T3-derived cell line. The use of sequence-specific, fluorescent RNA molecules permits the concomitant determination of their subcellular localization and biological functions. We also outline adaptations of RATaR when implemented in different cell lines exposed to various genotoxic treatments, such as γ-radiation, restriction enzymes and telomere deprotection. In all these cases, the entire procedure can be completed within 2 h without the need for special equipment or uncommon skills. We believe this technique will prove useful for investigating the contribution of RNA to a variety of relevant cellular processes.


Assuntos
Dano ao DNA , Reparo do DNA , RNA não Traduzido , Ribonuclease Pancreático/metabolismo , Animais , Dano ao DNA/genética , Dano ao DNA/fisiologia , Reparo do DNA/genética , Reparo do DNA/fisiologia , Técnicas Genéticas , Células HeLa , Humanos , Camundongos , Células NIH 3T3 , RNA/análise , RNA/genética , RNA/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/fisiologia
4.
Arch Pharm Res ; 42(1): 48-62, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30610616

RESUMO

Hepatocellular carcinoma (HCC) is a tumor with poor prognosis and frequently aggressive. The development of HCC is associated with fibrosis and cirrhosis, which mainly results from nonalcoholic fatty liver disease, excessive alcohol consumption, and viral infections. Non-coding RNAs (ncRNAs) are RNAs transcribed from the genome, but are not translated into proteins. Recently, ncRNAs emerged as key contributors to tumor development and progression because of their abilities to regulate various targets and modulate cell proliferation, differentiation, apoptosis, and development. In this review, we summarize the frequently activated pathways in HCC and discuss the pathological implications of ncRNAs in the context of human liver disease progression, in particular HCC development and progression. This review aims to summarize the role of ncRNA dysregulation in the diseases and discuss the diagnostic and therapeutic potentials of ncRNAs.


Assuntos
Carcinoma Hepatocelular/metabolismo , Progressão da Doença , Hepatopatias/metabolismo , Neoplasias Hepáticas/metabolismo , RNA não Traduzido/fisiologia , Animais , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Humanos , Hepatopatias/patologia , Neoplasias Hepáticas/patologia , RNA Longo não Codificante/fisiologia , Transdução de Sinais/fisiologia
5.
Annu Rev Entomol ; 64: 185-203, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30285490

RESUMO

Epigenetic inheritance is fundamentally important to cellular differentiation and developmental plasticity. In this review, we provide an introduction to the field of molecular epigenetics in insects. Epigenetic information is passed across cell divisions through the methylation of DNA, the modification of histone proteins, and the activity of noncoding RNAs. Much of our knowledge of insect epigenetics has been gleaned from a few model species. However, more studies of epigenetic information in traditionally nonmodel taxa will help advance our understanding of the developmental and evolutionary significance of epigenetic inheritance in insects. To this end, we also provide a brief overview of techniques for profiling and perturbing individual facets of the epigenome. Doing so in diverse cellular, developmental, and taxonomic contexts will collectively help shed new light on how genome regulation results in the generation of diversity in insect form and function.


Assuntos
Metilação de DNA , Epigênese Genética , Código das Histonas , Insetos/genética , RNA não Traduzido/fisiologia , Animais , Fenótipo
6.
BMB Rep ; 52(1): 86-108, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30526773

RESUMO

In multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and gene expression has been observed to be deregulated with aging. In this review, we discuss the current knowledge on the transcriptional alterations that have been described to occur with age in metazoans. First, we discuss age-related transcriptional changes in protein-coding genes, the expected functional impact of such changes, and how known pro-longevity interventions impact these changes. Second, we discuss the changes and impact of emerging aspects of transcription in aging, including age-related changes in splicing, lncRNAs and circRNAs. Third, we discuss the changes and potential impact of transcription of transposable elements with aging. Fourth, we highlight small ncRNAs and their potential impact on the regulation of aging phenotypes. Understanding the aging transcriptome will be key to identify important regulatory targets, and ultimately slow-down or reverse aging and extend healthy lifespan in humans. [BMB Reports 2019; 52(1): 86-108].


Assuntos
Envelhecimento/genética , Longevidade/genética , Transcriptoma/genética , Animais , Expressão Gênica/genética , Regulação da Expressão Gênica/fisiologia , Homeostase , Humanos , Fenótipo , RNA não Traduzido/genética , RNA não Traduzido/fisiologia
7.
Plant Biotechnol J ; 17(1): 302-315, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29947466

RESUMO

Lignin provides structural support in perennial woody plants and is a complex phenolic polymer derived from phenylpropanoid pathway. Lignin biosynthesis is regulated by coordinated networks involving transcription factors (TFs), microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). However, the genetic networks underlying the lignin biosynthesis pathway for tree growth and wood properties remain unknown. Here, we used association genetics (additive, dominant and epistasis) and expression quantitative trait nucleotide (eQTN) mapping to decipher the genetic networks for tree growth and wood properties in 435 unrelated individuals of Populus tomentosa. We detected 124 significant associations (P ≤ 6.89E-05) for 10 growth and wood property traits using 30 265 single nucleotide polymorphisms from 203 lignin biosynthetic genes, 81 TF genes, 36 miRNA genes and 71 lncRNA loci, implying their common roles in wood formation. Epistasis analysis uncovered 745 significant pairwise interactions, which helped to construct proposed genetic networks of lignin biosynthesis pathway and found that these regulators might affect phenotypes by linking two lignin biosynthetic genes. eQTNs were used to interpret how causal genes contributed to phenotypes. Lastly, we investigated the possible functions of the genes encoding 4-coumarate: CoA ligase and cinnamate-4-hydroxylase in wood traits using epistasis, eQTN mapping and enzymatic activity assays. Our study provides new insights into the lignin biosynthesis pathway in poplar and enables the novel genetic factors as biomarkers for facilitating genetic improvement of trees.


Assuntos
Genes de Plantas/genética , Lignina/biossíntese , Populus/genética , RNA não Traduzido/genética , Fatores de Transcrição/genética , Madeira/crescimento & desenvolvimento , Genes de Plantas/fisiologia , Desequilíbrio de Ligação/genética , Redes e Vias Metabólicas/genética , MicroRNAs/genética , MicroRNAs/fisiologia , Polimorfismo de Nucleotídeo Único/genética , Populus/crescimento & desenvolvimento , Populus/metabolismo , Locos de Características Quantitativas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , RNA não Traduzido/fisiologia , Fatores de Transcrição/fisiologia , Transcriptoma , Madeira/metabolismo
8.
Oncol Res ; 27(2): 219-226, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-29562954

RESUMO

Breast cancer (BC) is the most common malignant tumor in women. Recently, long noncoding RNAs (lncRNAs) have been proposed as critical regulators in biological processes, including tumorigenesis. FOXC2-AS1, a single antisense oligonucleotide RNA transcribed from the negative strand of forkhead box protein C2 (FOXC2), has been identified as an oncogene in osteosarcoma. In the present study, we investigated the prognosis value and biological role of FOXC2-AS1 in BC. Our findings revealed that FOXC2-AS1 was significantly increased in BC tissues and cell lines, and Kaplan-Meier survival analysis indicated that a high level of FOXC2-AS1 was associated with poor prognosis of BC patients. Loss of function revealed that silenced FOXC2-AS1 significantly suppressed the proliferation ability, and flow cytometric analysis illustrated the influence of FOXC2-AS1 on cell cycle and apoptosis rate. Finally, we found that cyclin D1, cyclin D2, and cyclin D3 were all partly positively modulated by FOXC2-AS1 in BC. Collectively, FOXC2-AS1 may serve as a promising prognostic biomarker and therapeutic target for BC patients.


Assuntos
Neoplasias da Mama/mortalidade , Fatores de Transcrição Forkhead/genética , Oligonucleotídeos Antissenso/metabolismo , Oncogenes/fisiologia , RNA Longo não Codificante/fisiologia , RNA não Traduzido/fisiologia , Apoptose , Neoplasias da Mama/etiologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Fatores de Transcrição Forkhead/fisiologia , Regulação Neoplásica da Expressão Gênica , Humanos
9.
Med Chem ; 15(3): 216-230, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30484409

RESUMO

BACKGROUND: Noncoding RNAs (ncRNAs) which play an important role in various cellular processes are important in medicine as well as in drug design strategies. Different studies have shown that ncRNAs are dis-regulated in cancer cells and play an important role in human tumorigenesis. Therefore, it is important to identify and predict such molecules by experimental and computational methods, respectively. However, to avoid expensive experimental methods, computational algorithms have been developed for accurately and fast prediction of ncRNAs. OBJECTIVE: The aim of this review was to introduce the experimental and computational methods to identify and predict ncRNAs structure. Also, we explained the ncRNA's roles in cellular processes and drugs design, briefly. METHOD: In this survey, we will introduce ncRNAs and their roles in biological and medicinal processes. Then, some important laboratory techniques will be studied to identify ncRNAs. Finally, the state-of-the-art models and algorithms will be introduced along with important tools and databases. RESULTS: The results showed that the integration of experimental and computational approaches improves to identify ncRNAs. Moreover, the high accurate databases, algorithms and tools were compared to predict the ncRNAs. CONCLUSION: ncRNAs prediction is an exciting research field, but there are different difficulties. It requires accurate and reliable algorithms and tools. Also, it should be mentioned that computational costs of such algorithm including running time and usage memory are very important. Finally, some suggestions were presented to improve computational methods of ncRNAs gene and structural prediction.


Assuntos
RNA não Traduzido , Algoritmos , Simulação por Computador , Bases de Dados Factuais , Desenho de Drogas , RNA não Traduzido/química , RNA não Traduzido/farmacologia , RNA não Traduzido/fisiologia
10.
Nat Struct Mol Biol ; 25(12): 1070-1076, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30420773

RESUMO

Although the number of documented noncoding RNAs (ncRNAs) is rapidly increasing, knowledge of their molecular function is lagging behind. The identification of specific RNA motifs that mediate transcript stability, interactions and localization may aid in the prediction of these features in new transcripts and may have potential implications for ncRNA function. Here, we review RNA motifs, focusing on four recent studies identifying nuclear-retention motifs, and discuss the limited specificity of short-RNA motifs and the resulting challenge for effective functional prediction. Future approaches may succeed by integrating combinatorial and cooperative effects of additional partially sequence-based properties.


Assuntos
Motivos de Nucleotídeos , RNA não Traduzido/química , Modelos Moleculares , Estabilidade de RNA , RNA não Traduzido/metabolismo , RNA não Traduzido/fisiologia
11.
Kidney Int ; 94(5): 870-881, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30348304

RESUMO

Acute kidney injury (AKI) is an important health issue concerning ∼50% of patients treated in intensive care units. AKI mainly occurs after sepsis, acute ischemia, nephrotoxicity, or hypoxia and leads to severe damage of the kidney and to an increased risk of mortality. The diagnosis of AKI is currently based on creatinine urea levels and diuresis. Yet, novel markers may improve the accuracy of this diagnosis at an early stage of the disease, thereby allowing early prevention and therapy, ultimately leading to a reduction in the need for renal replacement therapy and decreased mortality. Non-protein-coding RNAs or noncoding RNAs are central players in development and disease. They are important regulatory molecules that allow a fine-tuning of gene expression and protein synthesis. This regulation is necessary to maintain homeostasis, and its dysregulation is often associated with disease development. Noncoding RNAs are present in the kidney and in body fluids and their expression is modulated during AKI. This review article assembles the current knowledge of the role of noncoding RNAs, including microRNAs, long noncoding RNAs and circular RNAs, in the pathogenesis of AKI. Their potential as biomarkers and therapeutic targets as well as the challenges to translate research findings to clinical application are discussed. Although microRNAs have entered clinical testing, preclinical and clinical trials are needed before long noncoding RNAs and circular RNAs may be considered as useful biomarkers or therapeutic targets of AKI.


Assuntos
Lesão Renal Aguda/genética , RNA não Traduzido/fisiologia , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/terapia , Animais , Biomarcadores , Humanos , MicroRNAs/fisiologia , RNA/fisiologia , RNA Longo não Codificante/fisiologia
12.
Arterioscler Thromb Vasc Biol ; 38(9): 1986-1996, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30354260

RESUMO

Endothelial-to-mesenchymal transition (EndMT) is a process in which endothelial cells lose their properties and transform into fibroblast-like cells. This transition process contributes to cardiac fibrosis, a common feature of patients with chronic heart failure. To date, no specific therapies to halt or reverse cardiac fibrosis are available, so knowledge of the underlying mechanisms of cardiac fibrosis is urgently needed. In addition, EndMT contributes to other cardiovascular pathologies such as atherosclerosis and pulmonary hypertension, but also to cancer and organ fibrosis. Remarkably, the molecular mechanisms driving EndMT are largely unknown. Epigenetics play an important role in regulating gene transcription and translation and have been implicated in the EndMT process. Therefore, epigenetics might be the missing link in unraveling the underlying mechanisms of EndMT. Here, we review the involvement of epigenetic regulators during EndMT in the context of cardiac fibrosis. The role of DNA methylation, histone modifications (acetylation and methylation), and noncoding RNAs (microRNAs, long noncoding RNAs, and circular RNAs) in the facilitation and inhibition of EndMT are discussed, and potential therapeutic epigenetic targets will be highlighted.


Assuntos
Epigênese Genética , Transição Epitelial-Mesenquimal , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/fisiopatologia , Acetilação , Doença Crônica , Metilação de DNA , Fibrose , Insuficiência Cardíaca/patologia , Histonas/metabolismo , Humanos , Metilação , RNA não Traduzido/fisiologia , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo
13.
BMC Cancer ; 18(1): 952, 2018 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-30286729

RESUMO

BACKGROUND: The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis in some cancers. However, the expression and biological role of T-UCRs in renal cell carcinoma (RCC) remain poorly understood. This study aimed to examine the expression and functional role of Uc.416 + A and analyze the association between Uc.416 + A and epithelial-to-mesenchymal transition in RCC. METHODS: Expression of Uc.416 + A in 35 RCC tissues, corresponding normal kidney tissues and 13 types of normal tissue samples was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). We performed a cell growth and migration assay in RCC cell line 786-O transfected with negative control and siRNA for Uc.416 + A. We evaluated the relation between Uc.416 + A and miR-153, which has a complimentary site of Uc.416 + A. RESULTS: qRT-PCR analysis revealed that the expression of Uc.416 + A was higher in RCC tissues than that in corresponding normal kidney tissues. Inhibition of Uc.416 + A reduced cell growth and cell migration activity. There was an inverse correlation between Uc.416 + A and miR-153. Western blot analysis showed Uc.416 + A modulated E-cadherin, vimentin and snail. The expression of Uc.416 + A was positively associated with the expression of SNAI1, VIM and inversely associated with the expression of CDH1. CONCLUSIONS: The expression of Uc.416 + A was upregulated in RCC and especially in RCC tissues with sarcomatoid change. Uc.416 + A promoted epithelial-to-mesenchymal transition through miR-153. These results suggest that Uc.416 + A may be a promising therapeutic target.


Assuntos
Carcinoma de Células Renais/metabolismo , Transição Epitelial-Mesenquimal/genética , Neoplasias Renais/metabolismo , MicroRNAs/fisiologia , RNA não Traduzido/metabolismo , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Humanos , RNA não Traduzido/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
Mol Cell ; 71(6): 1051-1063.e6, 2018 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-30174290

RESUMO

Protein kinase RNA-activated (PKR) induces immune response by sensing viral double-stranded RNAs (dsRNAs). However, growing evidence suggests that PKR can also be activated by endogenously expressed dsRNAs. Here, we capture these dsRNAs by formaldehyde-mediated crosslinking and immunoprecipitation sequencing and find that various noncoding RNAs interact with PKR. Surprisingly, the majority of the PKR-interacting RNA repertoire is occupied by mitochondrial RNAs (mtRNAs). MtRNAs can form intermolecular dsRNAs owing to bidirectional transcription of the mitochondrial genome and regulate PKR and eIF2α phosphorylation to control cell signaling and translation. Moreover, PKR activation by mtRNAs is counteracted by PKR phosphatases, disruption of which causes apoptosis from PKR overactivation even in uninfected cells. Our work unveils dynamic regulation of PKR even without infection and establishes PKR as a sensor for nuclear and mitochondrial signaling cues in regulating cellular metabolism.


Assuntos
eIF-2 Quinase/metabolismo , eIF-2 Quinase/fisiologia , Linhagem Celular , Núcleo Celular , Ativação Enzimática , Fator de Iniciação 2 em Eucariotos/metabolismo , Células HEK293 , Células HeLa , Humanos , Imunoprecipitação/métodos , Mitocôndrias/genética , Fosforilação , RNA de Cadeia Dupla/genética , RNA Mitocondrial/genética , RNA Mitocondrial/fisiologia , RNA não Traduzido/genética , RNA não Traduzido/fisiologia , Transdução de Sinais , eIF-2 Quinase/imunologia
15.
J Virol ; 92(20)2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30068655

RESUMO

Viroids are circular noncoding RNAs (ncRNAs) that infect plants. Despite differences in the genetic makeup and biogenesis, viroids and various long ncRNAs all rely on RNA structure-based interactions with cellular factors for function. Viroids replicating in the nucleus utilize DNA-dependent RNA polymerase II for transcription, a process that involves a unique splicing form of transcription factor IIIA (TFIIIA-7ZF). Here, we provide evidence showing that potato spindle tuber viroid (PSTVd) interacts with a TFIIIA splicing regulator (ribosomal protein L5 [RPL5]) in vitro and in vivo PSTVd infection compromises the regulatory role of RPL5 over splicing of TFIIIA transcripts, while ectopic expression of RPL5 reduces TFIIIA-7ZF expression and attenuates PSTVd accumulation. Furthermore, we illustrate that the RPL5 binding site on the PSTVd genome resides in the central conserved region critical for replication. Together, our data suggest that viroids can regulate their own replication and modulate specific regulatory factors leading to splicing changes in only one or a few genes. This study also has implications for understanding the functional mechanisms of ncRNAs and elucidating the global splicing changes in various host-pathogen interactions.IMPORTANCE Viroids are the smallest replicons among all living entities. As circular noncoding RNAs, viroids can replicate and spread in plants, often resulting in disease symptoms. Potato spindle tuber viroid (PSTVd), the type species of nuclear-replicating viroids, requires a unique splicing form of transcription factor IIIA (TFIIIA-7ZF) for its propagation. Here, we provide evidence showing that PSTVd directly interacts with a splicing regulator, RPL5, to favor the expression of TFIIIA-7ZF, thereby promoting viroid replication. This finding provides new insights to better understand viroid biology and sheds light on the noncoding RNA-based regulation of splicing. Our discovery also establishes RPL5 as a novel negative factor regulating viroid replication in the nucleus and highlights a potential means for viroid control.


Assuntos
RNA não Traduzido/fisiologia , Proteínas Ribossômicas/metabolismo , Solanum tuberosum/virologia , Viroides/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Vírus de Plantas/fisiologia , RNA Polimerase II/metabolismo , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Fator de Transcrição TFIIIA/genética , Replicação Viral
16.
Microbiol Spectr ; 6(4)2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29992899

RESUMO

Bacterial noncoding RNA (ncRNA) classes longer than 200 nucleotides are rare but are responsible for performing some of the most fundamental tasks in living cells. RNAs such as 16S and 23S rRNA, group I and group II introns, RNase P ribozymes, transfer-messenger RNAs, and coenzyme B12 riboswitches are diverse in structure and accomplish biochemical functions that rival the activities of proteins. Over the last decade, a number of new classes of large ncRNAs have been uncovered in bacteria. A total of 21 classes with no established functions have been identified through the use of bioinformatics search strategies. Based on precedents for bacterial large ncRNAs performing sophisticated functions, it seems likely that some of these structured ncRNAs also will prove to carry out complex functions. Thus, determining their roles will provide a better understanding of fundamental biological processes. A few studies have produced data that provide clues to the purposes of some of these recently found classes, but the true functions of most classes remain mysterious.


Assuntos
Bactérias/genética , Bactérias/metabolismo , Fenômenos Fisiológicos Bacterianos , RNA não Traduzido/classificação , RNA não Traduzido/fisiologia , Sequência de Bases , Biologia Computacional , Regulação Bacteriana da Expressão Gênica , Conformação de Ácido Nucleico , RNA Bacteriano/genética , RNA Bacteriano/fisiologia , RNA não Traduzido/genética
17.
Mol Reprod Dev ; 85(8-9): 720-728, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29969526

RESUMO

Spermatogonial stem cells (SSCs), a unique population of male germ cells with self-renewal ability, are the foundation for maintenance of spermatogenesis throughout the life of the male. Although many regulatory molecules essential for SSC self-renewal have been identified, the fundamental mechanism underlying how SSCs acquire and maintain their self-renewal activity remains largely to be elucidated. In recent years, many types of noncoding RNAs (ncRNAs) have been suggested to regulate the SSC self-renewal through multiple ways, indicating ncRNAs play crucial roles in SSC self-renewal. In this paper, we mainly focus on four types of ncRNAs including microRNA, long ncRNA, piwi-interacting RNA, as well as circular RNAs, and reviewed their potential roles in SSC self-renewal that discovered recently to help us gain a better understanding of molecular mechanisms by which ncRNAs perform their function in regulating SSC self-renewal.


Assuntos
Células-Tronco Germinativas Adultas/fisiologia , Proliferação de Células/fisiologia , RNA não Traduzido/fisiologia , Espermatogênese/fisiologia , Animais , Fatores Neurotróficos Derivados de Linhagem de Célula Glial/fisiologia , Humanos , Masculino , Mamíferos , Camundongos
18.
Adv Exp Med Biol ; 1012: 49-59, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29956194

RESUMO

According to the DOHaD theory, low birth weight is a risk factor for various noncommunicable chronic diseases that develop later in life. Noncoding RNAs (ncRNAs), including miRNAs, siRNAs, piRNAs, and lncRNAs, are functional RNA molecules that are transcribed from DNA but that are not translated into proteins. In general, miRNAs, siRNAs, and piRNAs function to regulate gene expression at the transcriptional and posttranscriptional levels. Studying ncRNAs has provided opportunities for new diagnosis and therapeutic knowledge in the endocrinological and metabolic fields as well as cancer biology. In this review, we focus on the roles of miRNAs and lncRNAs in the pathophysiology of stress-related neuropsychiatric diseases, which show abnormal blood hormone levels due to loss of feedback control and/or decreased sensitivity. Numerous recent studies have begun to unveil the importance of ncRNAs in regulation of stress-related hormone levels and functions. We summarize the involvement of abnormal ncRNA expression in the development of stress-related neuropsychiatric diseases based on the DOHaD theory.


Assuntos
Transtornos Mentais/etiologia , Complicações na Gravidez/psicologia , Efeitos Tardios da Exposição Pré-Natal , RNA não Traduzido/fisiologia , Estresse Psicológico/complicações , Estresse Psicológico/genética , Animais , Feminino , Humanos , Transtornos Mentais/genética , Gravidez , Complicações na Gravidez/genética , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/psicologia
19.
Circ Res ; 122(11): 1586-1607, 2018 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-29798902

RESUMO

If unifying principles could be revealed for how the same genome encodes different eukaryotic cells and for how genetic variability and environmental input are integrated to impact cardiovascular health, grand challenges in basic cell biology and translational medicine may succumb to experimental dissection. A rich body of work in model systems has implicated chromatin-modifying enzymes, DNA methylation, noncoding RNAs, and other transcriptome-shaping factors in adult health and in the development, progression, and mitigation of cardiovascular disease. Meanwhile, deployment of epigenomic tools, powered by next-generation sequencing technologies in cardiovascular models and human populations, has enabled description of epigenomic landscapes underpinning cellular function in the cardiovascular system. This essay aims to unpack the conceptual framework in which epigenomes are studied and to stimulate discussion on how principles of chromatin function may inform investigations of cardiovascular disease and the development of new therapies.


Assuntos
Doenças Cardiovasculares/genética , Cromatina/fisiologia , Epigênese Genética/fisiologia , Epigenômica/tendências , Doenças Cardiovasculares/terapia , Fenômenos Fisiológicos Cardiovasculares , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Cromatina/genética , Montagem e Desmontagem da Cromatina/fisiologia , Metilação de DNA/fisiologia , Epigenômica/métodos , Interação Gene-Ambiente , Predisposição Genética para Doença , Histona Desacetilases/fisiologia , Histonas/fisiologia , Humanos , Nucleossomos/genética , Nucleossomos/fisiologia , RNA não Traduzido/fisiologia , Transcriptoma
20.
Biochem Soc Trans ; 46(3): 619-630, 2018 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-29743276

RESUMO

Non-coding RNAs (ncRNAs) are an abundant class of RNAs that include small ncRNAs, long non-coding RNAs (lncRNA) and pseudogenes. The human ncRNA atlas includes thousands of these specialised RNA molecules that are further subcategorised based on their size or function. Two of the more well-known and widely studied ncRNA species are microRNAs (miRNAs) and lncRNAs. These are regulatory RNAs and their altered expression has been implicated in the pathogenesis of a variety of human diseases. Failure to express a functional cystic fibrosis (CF) transmembrane receptor (CFTR) chloride ion channel in epithelial cells underpins CF. Secondary to the CFTR defect, it is known that other pathways can be altered and these may contribute to the pathophysiology of CF lung disease in particular. For example, quantitative alterations in expression of some ncRNAs are associated with CF. In recent years, there has been a series of published studies exploring ncRNA expression and function in CF. The majority have focussed principally on miRNAs, with just a handful of reports to date on lncRNAs. The present study reviews what is currently known about ncRNA expression and function in CF, and discusses the possibility of applying this knowledge to the clinical management of CF in the near future.


Assuntos
Fibrose Cística/genética , RNA não Traduzido/fisiologia , Animais , Fibrose Cística/metabolismo , Fibrose Cística/fisiopatologia , Fibrose Cística/terapia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Humanos , Imunidade Inata/genética , Inflamação/genética , MicroRNAs/fisiologia , Pseudogenes , Resposta a Proteínas não Dobradas
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