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1.
Nat Commun ; 11(1): 6439, 2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33353944

RESUMO

During oocyte growth, transcription is required to create RNA and protein reserves to achieve maternal competence. During this period, the general transcription factor TATA binding protein (TBP) is replaced by its paralogue, TBPL2 (TBP2 or TRF3), which is essential for RNA polymerase II transcription. We show that in oocytes TBPL2 does not assemble into a canonical TFIID complex. Our transcript analyses demonstrate that TBPL2 mediates transcription of oocyte-expressed genes, including mRNA survey genes, as well as specific endogenous retroviral elements. Transcription start site (TSS) mapping indicates that TBPL2 has a strong preference for TATA-like motif in core promoters driving sharp TSS selection, in contrast with canonical TBP/TFIID-driven TATA-less promoters that have broader TSS architecture. Thus, we show a role for the TBPL2/TFIIA complex in the establishment of the oocyte transcriptome by using a specific TSS recognition code.


Assuntos
Proteínas Nucleares/metabolismo , Oócitos/metabolismo , Regiões Promotoras Genéticas , Fator de Transcrição TFIIA/metabolismo , Transcriptoma/genética , Animais , Animais Recém-Nascidos , Feminino , Regulação da Expressão Gênica , Camundongos , Camundongos Endogâmicos C57BL , Mutação/genética , Células NIH 3T3 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , TATA Box , Sequências Repetidas Terminais/genética , Fator de Transcrição TFIID/metabolismo , Transcrição Genética
2.
Proc Natl Acad Sci U S A ; 117(31): 18701-18710, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32690679

RESUMO

Yin Yang 1 (YY1) is a DNA-binding transcription factor that either activates or represses gene expression. YY1 has previously been implicated in the transcriptional silencing of many retroviruses by binding to DNA sequences in the U3 region of the viral long terminal repeat (LTR). We here show that YY1 overexpression leads to profound activation, rather than repression, of human T lymphotropic virus type 1 (HTLV-1) expression, while YY1 down-regulation reduces HTLV-1 expression. The YY1 responsive element mapped not to YY1 DNA-binding sites in the HTLV-1 LTR but to the R region. The HTLV-1 R sequence alone is sufficient to provide YY1 responsiveness to a nonresponsive promoter, but only in the sense orientation and only when included as part of the mRNA. YY1 binds to the R region of HTLV-1 RNA in vitro and in vivo, leading to increased transcription initiation and elongation. The findings indicate that YY1 is a potent transactivator of HTLV-1 gene expression acting via binding viral RNA, rather than DNA.


Assuntos
Regulação Viral da Expressão Gênica/genética , Vírus Linfotrópico T Tipo 1 Humano , RNA/metabolismo , Sequências Repetidas Terminais/genética , Fator de Transcrição YY1 , Células HEK293 , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/metabolismo , Humanos , Células Jurkat , Ligação Proteica/genética , RNA/genética , Ativação Transcricional/genética , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismo
3.
Proc Natl Acad Sci U S A ; 117(27): 15763-15771, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32571938

RESUMO

HIV-1 latency is a major barrier to cure. Identification of small molecules that destabilize latency and allow immune clearance of infected cells could lead to treatment-free remission. In vitro models of HIV-1 latency involving cell lines or primary cells have been developed for characterization of HIV-1 latency and high-throughput screening for latency-reversing agents (LRAs). We have shown that the majority of LRAs identified to date are relatively ineffective in cells from infected individuals despite activity in model systems. We show here that, for diverse LRAs, latency reversal observed in model systems involves a heat shock factor 1 (HSF1)-mediated stress pathway. Small-molecule inhibition of HSF1 attenuated HIV-1 latency reversal by histone deactylase inhibitors, protein kinase C agonists, and proteasome inhibitors without interfering with the known mechanism of action of these LRAs. However, latency reversal by second mitochondria-derived activator of caspase (SMAC) mimetics was not affected by inhibition of HSF1. In cells from infected individuals, inhibition of HSF1 attenuated latency reversal by phorbol ester+ionomycin but not by anti-CD3+anti-CD28. HSF1 promotes elongation of HIV-1 RNA by recruiting P-TEFb to the HIV-1 long terminal repeat (LTR), and we show that inhibition of HSF1 attenuates the formation of elongated HIV-1 transcripts. We demonstrate that in vitro models of latency have higher levels of the P-TEFb subunit cyclin T1 than primary cells, which may explain why many LRAs are functional in model systems but relatively ineffective in primary cells. Together, these studies provide insights into why particular LRA combinations are effective in reversing latency in cells from infected individuals.


Assuntos
Infecções por HIV/genética , HIV-1/genética , Fatores de Transcrição de Choque Térmico/genética , Latência Viral/genética , Fármacos Anti-HIV/farmacologia , Proteínas Reguladoras de Apoptose/genética , Ciclina T/genética , Infecções por HIV/virologia , HIV-1/patogenicidade , Fatores de Transcrição de Choque Térmico/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Humanos , Proteínas Mitocondriais/genética , Fator B de Elongação Transcricional Positiva/genética , Proteína Quinase C/genética , RNA Viral/efeitos dos fármacos , RNA Viral/genética , Bibliotecas de Moléculas Pequenas/farmacologia , Sequências Repetidas Terminais/genética , Ativação Viral/genética
4.
Sci Rep ; 10(1): 7720, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382084

RESUMO

Genome dynamics was investigated within natural populations of the soil bacterium Streptomyces. The exploration of a set of closely related strains isolated from micro-habitats of a forest soil exhibited a strong diversity of the terminal structures of the linear chromosome, i.e. terminal inverted repeats (TIRs). Large insertions, deletions and translocations could be observed along with evidence of transfer events between strains. In addition, the telomere and its cognate terminal protein complexes required for terminal replication and chromosome maintenance, were shown to be variable within the population probably reflecting telomere exchanges between the chromosome and other linear replicons (i.e., plasmids). Considering the close genetic relatedness of the strains, these data suggest that the terminal regions are prone to a high turnover due to a high recombination associated with extensive horizontal gene transfer.


Assuntos
Cromossomos Bacterianos/genética , Replicação do DNA/genética , Streptomyces/genética , Telômero/genética , Sequência de Aminoácidos/genética , Variação Genética , Plasmídeos/genética , Recombinação Genética/genética , Replicon/genética , Microbiologia do Solo , Sequências Repetidas Terminais/genética
5.
Proc Natl Acad Sci U S A ; 117(11): 5987-5996, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32123111

RESUMO

Endogenous retroviruses and long terminal repeat (LTR) retrotransposons are mobile genetic elements that are closely related to retroviruses. Desilenced endogenous retroviruses are associated with human autoimmune disorders and neurodegenerative diseases. Caenorhabditis elegans and related Caenorhabditis spp. contain LTR retrotransposons and, as described here, numerous integrated viral genes including viral envelope genes that are part of LTR retrotransposons. We found that both LTR retrotransposons and endogenous viral elements are silenced by ADARs [adenosine deaminases acting on double-stranded RNA (dsRNA)] together with the endogenous RNA interference (RNAi) factor ERI-6/7, a homolog of MOV10 helicase, a retrotransposon and retrovirus restriction factor in human. siRNAs corresponding to integrated viral genes and LTR retrotransposons, but not to DNA transposons, are dependent on the ADARs and ERI-6/7. siRNAs corresponding to palindromic repeats are independent of the ADARs and ERI-6/7, and are in fact increased in adar- and eri-6/7-defective mutants because of an antiviral RNAi response to dsRNA. Silencing of LTR retrotransposons is dependent on downstream RNAi factors and P granule components but is independent of the viral sensor DRH-1/RIG-I and the nuclear Argonaute NRDE-3. The activation of retrotransposons in the ADAR- and ERI-6/7/MOV10-defective mutant is associated with the induction of the unfolded protein response (UPR), a common response to viral infection. The overlap between genes induced upon viral infection and infection with intracellular pathogens and genes coexpressed with retrotransposons suggests that there is a common response to different types of foreign elements that includes a response to proteotoxicity presumably caused by the burden of replicating pathogens and expressed retrotransposons.


Assuntos
Caenorhabditis elegans/genética , Retrovirus Endógenos/genética , Interações entre Hospedeiro e Microrganismos/genética , Interferência de RNA , Retroelementos/genética , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismo , Animais , Caenorhabditis elegans/virologia , Proteínas de Caenorhabditis elegans/metabolismo , DNA Helicases/metabolismo , DNA Viral/metabolismo , Estresse do Retículo Endoplasmático/genética , Regulação Viral da Expressão Gênica , Genes Virais/genética , Humanos , RNA de Cadeia Dupla/metabolismo , RNA Viral/metabolismo , Homologia de Sequência de Aminoácidos , Sequências Repetidas Terminais/genética , Resposta a Proteínas não Dobradas/genética
6.
Nat Commun ; 11(1): 1221, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144266

RESUMO

Silencing of transposable elements (TEs) is established by small RNA-directed DNA methylation (RdDM). Maintenance of silencing is then based on a combination of RdDM and RNA-independent mechanisms involving DNA methyltransferase MET1 and chromodomain DNA methyltransferases (CMTs). Involvement of RdDM, according to this model should decrease with TE age but here we show a different pattern in tomato and Arabidopsis. In these species the CMTs silence long terminal repeat (LTR) transposons in the distal chromatin that are younger than those affected by RdDM. To account for these findings we propose that, after establishment of primary RdDM as in the original model, there is an RNA-independent maintenance phase involving CMTs followed by secondary RdDM. This progression of epigenetic silencing in the gene-rich distal chromatin is likely to influence the transcriptome either in cis or in trans depending on whether the mechanisms are RNA-dependent or -independent.


Assuntos
Metilação de DNA/genética , Elementos de DNA Transponíveis/genética , Nucleotídeos/genética , Sistemas CRISPR-Cas/genética , Cromatina/metabolismo , Evolução Molecular , Inativação Gênica , Lycopersicon esculentum/genética , Lycopersicon esculentum/crescimento & desenvolvimento , Mutação/genética , Fenótipo , Proteínas de Plantas/metabolismo , RNA Polimerase II/metabolismo , Sequências Repetidas Terminais/genética
7.
Genetica ; 148(1): 13-23, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31960179

RESUMO

Long terminal repeats (LTR) retrotransposons have a major role in determining genome size, structure and function, thanks to their ability to transpose. We performed a meta-analysis of LTR-retrotransposon expression in roots of sunflower plantlets treated with different plant hormones, chemicals and NaCl. By using Illumina cDNA libraries, available from public repositories, we measured the number of reads matching the retrotranscriptase domains isolated from a whole genome library of retrotransposons. LTR-retrotransposons resulted in general barely expressed, except for 4 elements, all belonging to the AleII lineage, which showed high transcription levels in roots of both control and treated plants. The expression of retrotransposons in treated plants was slightly higher than in the control. Transcribed elements belonged to specific chromosomal loci and were not abundant in the genome. A few elements resulted differentially expressed depending on the treatment. Results suggest that, although most retrotransposons are not expressed, the transcription of such elements is related to their abundance, to their position in the chromosome and to their lineage.


Assuntos
Helianthus/genética , Retroelementos/genética , Sequências Repetidas Terminais/genética , Evolução Molecular , Regulação da Expressão Gênica de Plantas/genética , Tamanho do Genoma/genética , Genoma de Planta/genética , Estudo de Associação Genômica Ampla/métodos , Filogenia , Raízes de Plantas
8.
J Gen Virol ; 101(3): 299-308, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31916930

RESUMO

Endogenous retroviruses (ERVs) are widespread in vertebrate genomes. The recent availability of whole eukaryotic genomes has enabled their characterization in many organisms, including Gallus gallus (red jungle fowl), the progenitor of the domesticated chicken. Our bioinformatics analysis of a G. gallus ERV previously designated GGERV20 identified 35 proviruses with complete long terminal repeats (LTRs) and gag-pol open reading frames (ORFs) in the Genome Reference Consortium Chicken Build 6a, of which 8 showed potential for translation of functional retroviral polyproteins, including the integrase and reverse transcriptase enzymes. No elements were discovered with an env gene. Fifteen loci had LTR sequences with 100 % identity, indicative of recent integration. Chicken embryo fibroblast RNA-seq datasets showed reads representing the entire length of the GGERV20 provirus, supporting their potential for expressing viral proteins. To investigate the possibility that GGERV20 elements may not be fixed in the genome, we assessed the integration status of five loci in a meat-type chicken. PCRs targeting a GGERV20 locus on G. gallus chromosome one (GGERV201-1) reproducibly amplified both LTRs and the preintegration state, indicating that the bird from which the DNA was sampled was hemizygous at this locus. The four other loci examined only produced the preintegration state amplicons. These results reveal that GGERV20 is not fixed in the G. gallus population, and taken together with the lack of mutations seen in several provirus LTRs and their transcriptional activity, suggest that GGERV20 retroviruses have recently been and continue to be active in the chicken genome.


Assuntos
Embrião de Galinha/virologia , Galinhas/virologia , Cromossomos/virologia , Retrovirus Endógenos/genética , Animais , Linhagem Celular , DNA Viral/genética , Proteínas de Fusão gag-pol/genética , Genes env , Loci Gênicos , Fases de Leitura Aberta/genética , Filogenia , Provírus/genética , RNA-Seq , Sequências Repetidas Terminais/genética , Ativação Transcricional/genética
9.
Mol Biol Rep ; 47(3): 1589-1603, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31919750

RESUMO

Maize is one of the world's most important crops and a model for grass genome research. Long terminal repeat (LTR) retrotransposons comprise most of the maize genome; their ability to produce new copies makes them efficient high-throughput genetic markers. Inter-retrotransposon-amplified polymorphisms (IRAPs) were used to study the genetic diversity of maize germplasm. Five LTR retrotransposons (Huck, Tekay, Opie, Ji, and Grande) were chosen, based on their large number of copies in the maize genome, whereas polymerase chain reaction primers were designed based on consensus LTR sequences. The LTR primers showed high quality and reproducible DNA fingerprints, with a total of 677 bands including 392 polymorphic bands showing 58% polymorphism between maize hybrid lines. These markers were used to identify genetic similarities among all lines of maize. Analysis of genetic similarity was carried out based on polymorphic amplicon profiles and genetic similarity phylogeny analysis. This diversity was expected to display ecogeographical patterns of variation and local adaptation. The clustering method showed that the varieties were grouped into three clusters differing in ecogeographical origin. Each of these clusters comprised divergent hybrids with convergent characters. The clusters reflected the differences among maize hybrids and were in accordance with their pedigree. The IRAP technique is an efficient high-throughput genetic marker-generating method.


Assuntos
Variação Genética , Genoma de Planta/genética , Polimorfismo Genético , Retroelementos/genética , Sequências Repetidas Terminais/genética , Zea mays/genética , DNA de Plantas/química , DNA de Plantas/genética , Eletroforese em Gel de Ágar , Filogenia , Sementes/genética , Análise de Sequência de DNA/métodos , Especificidade da Espécie , Zea mays/classificação
10.
Genes Genomics ; 42(1): 55-65, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31721105

RESUMO

BACKGROUND: Sebastes schlegelii are an important species of fish found in the coastal areas of the Korea with significant commercial importance. Most studies thus far have been primarily focused on environmental factors; behavioural patterns, aquaculture, diseases and limited genetic studies with little to none related to either microRNAs (miRNAs) or transposable elements (TE). OBJECTIVES: In order to understand biological roles of TE-derived miR-1269a, we examined expression pattern for miR-1269a and its target gene, KSR2, in various tissues of Sebastes schlegelii. Also, we performed luciferase reporter assay in HINAE cells. METHODS: UCSC Genome Browser (https://genome.ucsc.edu/) was used to examine which TE is associated with miR-1269a. For the target genes for miR-1269a, the target genes associated with the miRNA were identified using miRDB (http://www.mirdb.org/) and TargetScan 7.1 (http://www.targetscan.org/vert_71/). A two-step miRNA kit, HB miR Multi Assay Kit™ System. I was used for the analysis of TE-derived miRNA expression patterns. The 3'UTR of KSR2 gene was cloned into the psiCHECK-2 vector. Subsequently co-transfected with miR-1269a mimics to HINAE cells for luciferase reporter assay. RESULTS: MiR-1269a was found to be derived from LTR retrotransposon, MLT2B. LTR-derived miR-1269a was highly expressed in the muscle, liver and gonad tissues of Sebastes schlegelii, but KSR2 revealed high expression in the brain. Co-transfection of KSR2 and miR-1269a mimic to HINAE cells showed high activity of miR-1269a in relation to KSR2. CONCLUSION: LTR-derived miR-1269a showed enhancer activity with relation to KSR2 in Sebastes schlegelii. The data may be used as a foundation for further investigation regarding correlation of miRNA and target genes in addition to other functional studies of biological significance in Sebastes schlegelii.


Assuntos
Regiões 3' não Traduzidas/genética , Proteínas de Peixes/metabolismo , MicroRNAs/genética , Perciformes/genética , Proteínas Serina-Treonina Quinases/metabolismo , Retroelementos/genética , Sequências Repetidas Terminais/genética , Animais , Sequência de Bases , Biologia Computacional , Proteínas de Peixes/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Proteínas Serina-Treonina Quinases/genética , Homologia de Sequência
11.
Mol Biotechnol ; 62(1): 31-42, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31673989

RESUMO

Pongamia pinnata (also called Millettia pinnata), a non-edible oil yielding tree, is well known for its multipurpose benefits and acts as a potential source for medicine and biodiesel preparation. Due to increase in demand for cultivation, understanding of genetic diversity is an important parameter for further breeding and cultivation programme. Transposable elements (TEs) are a major component of plant genome but still, their evolutionary significance in Pongamia remains unexplored. In view to understand the role of TEs in genome diversity, Pongamia unigenes were screened for the presence of TE cassettes. Our analysis showed the presence of all categories of TE cassettes in unigenes with major contribution of long terminal repeat-retrotransposons towards unigene diversity. Interestingly, the insertion of some TEs was also observed in both organellar genomes. The study of insertion of TEs in coding sequence is of great interest as they may be responsible for protein diversity thereby influencing the phenotype. The present investigation confirms the exaptation phenomenon in pyruvate decarboxylase (PDC) gene where the entire exon sequence was derived from Ty3-gypsy like retrotransposon. The study of PDC protein revealed the translation of gypsy element into protein. Furthermore, the phylogenetic study confirmed the diversity in PDC gene due to insertion of the gypsy element, where the PDC genes with and without gypsy insertion were clustered separately.


Assuntos
Genoma de Planta/genética , Pongamia/genética , Piruvato Descarboxilase/genética , Retroelementos/genética , Elementos de DNA Transponíveis/genética , Evolução Molecular , Éxons/genética , Genes de Cloroplastos , Genes Mitocondriais , Fases de Leitura Aberta , Filogenia , Pongamia/metabolismo , Sequências Repetidas Terminais/genética , Transcriptoma/genética
12.
Mol Genet Genomics ; 295(1): 47-54, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31420737

RESUMO

Stem trichomes and seed fibers originate from epidermal cells and partially share a regulatory pathway at the molecular level. In Gossypium barbadense, two insertions of a Ty1 long-terminal repeat-retrotransposon [transposable element TE1 and TE2] in a homeodomain-leucine zipper gene (HD1) result in glabrous stems. The primers used to identify the TE insertions in G. barbadense were applied to screen for the same events in 81 modern G. hirsutum varieties and 31 wild races. Three wild races were found carrying the same TEs as G. barbadense. However, the TE insertions in two of these wild races occurred at different sites (4th exon), therefore, named TE3, while the TE in the other wild race occurred at the same site as TE2. An RNA sequencing and qRT-PCR analysis indicated that the loss of HD1 function was caused by the TE insertion. Genetic mapping revealed a strong association between glabrous stems and TE3 insertions, confirming that HD1 is a critical gene for stem trichome initiation in G. hirsutum, as in G. barbadense. Using the long-terminal repeat sequence as a query to search against the Texas Marker-1 reference genome sequence, we found that the TE occurred after tetraploid cotton formation and evolved at different rates in G. hirsutum and G. barbadense. Interestingly, at least three independent insertion events of the same retrotransposon occurred preferentially in the A sub-genome's HD1 gene, but not in the D sub-genome of G. hirsutum or G. barbadense, suggesting that an unknown TE insertion mechanism and resultant gene function changes may have hastened cotton speciation.


Assuntos
Proteínas de Arabidopsis/genética , Gossypium/genética , Histona Desacetilases/genética , Mutagênese Insercional/genética , Caules de Planta/genética , Retroelementos/genética , Sequências Repetidas Terminais/genética , Tricomas/genética , Mapeamento Cromossômico/métodos , Regulação da Expressão Gênica de Plantas/genética , Genoma de Planta/genética , Zíper de Leucina/genética , Fenótipo , Filogenia , Tetraploidia
13.
Cancer Res ; 80(5): 976-987, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31874857

RESUMO

Long terminal repeat (LTR) retrotransposons are a major class of transposable elements, accounting for 8.67% of the human genome. LTRs can serve as regulatory sequences and drive transcription of tissue or cancer-specific transcripts. However, the role of these LTR-activated transcripts, especially long non-coding RNAs (lncRNA), in cancer development remains largely unexplored. Here, we identified a novel lncRNA derived from MER52A retrotransposons (lncMER52A) that was exclusively expressed in hepatocellular carcinoma (HCC). HCC patients with higher lncMER52A had advanced TNM stage, less differentiated tumors, and shorter overall survival. LncMER52A promoted invasion and metastasis of HCC cells in vitro and in vivo. Mechanistically, lncMER52A stabilized p120-catenin and triggered the activation of Rho GTPase downstream of p120-catenin. Furthermore, we found that chromatin accessibility was crucial for the expression of lncMER52A. In addition, YY1 transcription factor bound to the cryptic MER52A LTR promoter and drove lncMER52A transcription in HCC. In conclusion, we identified an LTR-activated lncMER52A, which promoted the progression of HCC cells via stabilizing p120-catenin and activating p120-ctn/Rac1/Cdc42 axis. LncMER52A could serve as biomarker and therapeutic target for patients with HCC. SIGNIFICANCE: A novel long noncoding RNA lncMER52 modulates cell migration and invasion via posttranslational control of p120-catenin protein stability. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/5/976/F1.large.jpg.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Cateninas/genética , Neoplasias Hepáticas/genética , RNA Longo não Codificante/metabolismo , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Fígado/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estabilidade Proteica , RNA Longo não Codificante/genética , RNA-Seq , Retroelementos/genética , Transdução de Sinais/genética , Sequências Repetidas Terminais/genética , Transcrição Genética , Fator de Transcrição YY1/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo
14.
Viruses ; 11(12)2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795223

RESUMO

Cells that are latently infected with HIV-1 preclude an HIV-1 cure, as antiretroviral therapy does not target this latent population. HIV-1 is highly genetically diverse, with over 10 subtypes and numerous recombinant forms circulating worldwide. In spite of this vast diversity, much of our understanding of latency and latency reversal is largely based on subtype B viruses. As such, most of the development of cure strategies targeting HIV-1 are solely based on subtype B. It is currently assumed that subtype does not influence the establishment or reactivation of latent viruses. However, this has not been conclusively proven one way or the other. A better understanding of the factors that influence HIV-1 latency in all viral subtypes will help develop therapeutic strategies that can be applied worldwide. Here, we review the latest literature on subtype-specific factors that affect viral replication, pathogenesis, and, most importantly, latency and its reversal.


Assuntos
Infecções por HIV/virologia , HIV-1/fisiologia , Latência Viral , Variação Genética , Geografia , HIV-1/classificação , HIV-1/genética , HIV-1/patogenicidade , Humanos , Sequências Repetidas Terminais/genética , Proteínas Virais/genética , Proteínas Virais/metabolismo , Replicação Viral
15.
Sci Rep ; 9(1): 19962, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882746

RESUMO

Terminal repeat retrotransposons in miniature (TRIMs) are small non-autonomous LTR retrotransposons consisting of two terminal direct repeats surrounding a short internal domain. The detection and characterization of these elements has been mainly limited to plants. Here we present the first finding of a TRIM element in bivalves, and among the first known in the kingdom Animalia. Class Bivalvia has high ecological and commercial importance in marine ecosystems and aquaculture, and, in recent years, an increasing number of genomic studies has addressed to these organisms. We have identified biv-TRIM in several bivalve species: Donax trunculus, Ruditapes decussatus, R. philippinarum, Venerupis corrugata, Polititapes rhomboides, Venus verrucosa, Dosinia exoleta, Glycymeris glycymeris, Cerastoderma edule, Magallana gigas, Mytilus galloprovincialis. biv-TRIM has several characteristics typical for this group of elements, exhibiting different variations. In addition to canonically structured elements, solo-TDRs and tandem repeats were detected. The presence of this element in the genome of each species is <1%. The phylogenetic analysis showed a complex clustering pattern of biv-TRIM elements, and indicates the involvement of horizontal transfer in the spreading of this element.


Assuntos
Bivalves/genética , Retroelementos/genética , Sequências Repetidas Terminais/genética , Animais , Evolução Biológica , Ecossistema , Evolução Molecular , Genoma , Filogenia
16.
Hum Gene Ther Methods ; 30(6): 206-213, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31752513

RESUMO

Ongoing development of recombinant vectors based on adeno-associated virus (rAAV) is providing an increasingly powerful and widely used toolkit for gene transfer and genome editing applications. While conceptually simple, the system harbors considerable complexity that presents many potential pitfalls for the inexperienced user. The short inverted terminal repeats (ITRs) can prove to be particularly problematic during vector engineering due to inherent instability necessitating diligent quality control measures during vector manufacture. This is especially important from a clinical standpoint when consistent purity and potency are paramount, and all components of the system are rigorously scrutinized by regulatory agencies. Despite the discovery over 30 years ago that the AAV ITRs are the only cis-acting elements of the virus required for vector production, there is a scarcity of reviews specifically focused on these complex elements. This review provides an overview of the ITR with the dual purpose of acting as a user's guide in the application of AAV vector technology and as a roadmap for ongoing vector development and optimization.


Assuntos
Dependovirus/genética , Vetores Genéticos/metabolismo , Sequências Repetidas Terminais/genética , Dependovirus/fisiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Conformação de Ácido Nucleico
17.
Genome Biol Evol ; 11(12): 3382-3392, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31755923

RESUMO

Transposable elements (TEs) are parasitic DNA bits capable of mobilization and mutagenesis, typically suppressed by host's epigenetic silencing. Since the selfish DNA concept, it is appreciated that genomes are also molded by arms-races against natural TE inhabitants. However, our understanding of evolutionary processes shaping TEs adaptive populations is scarce. Here, we review the events of recombination associated to reverse-transcription in LTR retrotransposons, a process shuffling their genetic variants during replicative mobilization. Current evidence may suggest that recombinogenic retrotransposons could beneficially exploit host suppression, where clan behavior facilitates their speciation and diversification. Novel refinements to retrotransposons life-cycle and evolution models thus emerge.


Assuntos
Recombinação Genética , Retroelementos/genética , Transcrição Reversa , Sequências Repetidas Terminais/genética , Epigênese Genética , Evolução Molecular , Inativação Gênica , Especiação Genética , Retroelementos/fisiologia , Seleção Genética
18.
BMC Bioinformatics ; 20(Suppl 9): 484, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31757208

RESUMO

BACKGROUND: Transposable Elements (TE) are mobile sequences that make up large portions of eukaryote genomes. The functions they play within the complex cellular architecture are still not clearly understood, but it is becoming evident that TE have a role in several physiological and pathological processes. In particular, it has been shown that TE transcription is necessary for the correct development of mice embryos and that their expression is able to finely modulate transcription of coding and non-coding genes. Moreover, their activity in the central nervous system (CNS) and other tissues has been correlated with the creation of somatic mosaicisms and with pathologies such as neurodevelopmental and neurodegenerative diseases as well as cancers. RESULTS: We analyzed TE expression among different cell types of the Caenorhabditis elegans (C. elegans) early embryo asking if, where and when TE are expressed and whether their expression is correlated with genes playing a role in early embryo development. To answer these questions, we took advantage of a public C. elegans embryonic single-cell RNA-seq (sc-RNAseq) dataset and developed a bioinformatics pipeline able to quantify reads mapping specifically against TE, avoiding counting reads mapping on TE fragments embedded in coding/non-coding transcripts. Our results suggest that i) canonical TE expression analysis tools, which do not discard reads mapping on TE fragments embedded in annotated transcripts, may over-estimate TE expression levels, ii) Long Terminal Repeats (LTR) elements are mostly expressed in undifferentiated cells and might play a role in pluripotency maintenance and activation of the innate immune response, iii) non-LTR are expressed in differentiated cells, in particular in neurons and nervous system-associated tissues, and iv) DNA TE are homogenously expressed throughout the C. elegans early embryo development. CONCLUSIONS: TE expression appears finely modulated in the C. elegans early embryo and different TE classes are expressed in different cell types and stages, suggesting that TE might play diverse functions during early embryo development.


Assuntos
Caenorhabditis elegans/embriologia , Caenorhabditis elegans/genética , Elementos de DNA Transponíveis/genética , Embrião não Mamífero/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Animais , Linhagem da Célula/genética , Biologia Computacional , Embrião não Mamífero/citologia , Desenvolvimento Embrionário/genética , Imunidade Inata/genética , Células-Tronco Pluripotentes/metabolismo , Sequências Repetidas Terminais/genética
19.
Genome Biol Evol ; 11(12): 3478-3495, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31710678

RESUMO

Speciation of the genus Citrus from a common ancestor has recently been established to begin ∼8 Ma during the late Miocene, a period of major climatic alterations. Here, we report the changes in activity of Citrus LTR retrotransposons during the process of diversification that gave rise to the current Citrus species. To reach this goal, we analyzed four pure species that diverged early during Citrus speciation, three recent admixtures derived from those species and an outgroup of the Citrus clade. More than 30,000 retrotransposons were grouped in ten linages. Estimations of LTR insertion times revealed that retrotransposon activity followed a species-specific pattern of change that could be ascribed to one of three different models. In some genomes, the expected pattern of gradual transposon accumulation was suddenly arrested during the radiation of the ancestor that gave birth to the current Citrus species. The individualized analyses of retrotransposon lineages showed that in each and every species studied, not all lineages follow the general pattern of the species itself. For instance, in most of the genomes, the retrotransposon activity of elements from the SIRE lineage reached its highest level just before Citrus speciation, while for Retrofit elements, it has been steadily growing. Based on these observations, we propose that Citrus retrotransposons may respond to stressful conditions driving speciation as a part of the genetic response involved in adaptation. This proposal implies that the evolving conditions of each species interact with the internal regulatory mechanisms of the genome controlling the proliferation of mobile elements.


Assuntos
Citrus/genética , Especiação Genética , Retroelementos/genética , Sequências Repetidas Terminais/genética , Citrus/classificação , Evolução Molecular , Genoma de Planta/genética , Modelos Genéticos , Filogenia , Especificidade da Espécie
20.
Sci Rep ; 9(1): 14007, 2019 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570746

RESUMO

Endogenous retroviruses (ERVs) have been identified at different copy numbers in various organisms. The long terminal repeat (LTR) element of an ERV has the capacity to exert regulatory influence as both a promoter and enhancer of cellular genes. Here, we describe olive flounder (OF)-ERV9, derived from chromosome 9 of the olive flounder. OF-ERV9-LTR provide binding sites for various transcription factors and showed enhancer activity. The OF-ERV9-LTR demonstrates high sequence similarity with the 3' untranslated region (UTR) of various genes that also contain seed sequences (TGTTTTG) that bind the LTR-derived microRNA(miRNA), OF-miRNA-307. Additionally, OF-miRNA-307 collaborates with transcription factors located in OF-ERV9-LTR to regulate gene expression. Taken together, our data facilitates a greater understanding of the molecular function of OF-ERV families and suggests that OF-miRNA-307 may act as a super-enhancer miRNA regulating gene activity.


Assuntos
Retrovirus Endógenos/genética , Linguado/virologia , MicroRNAs/genética , Sequências Repetidas Terminais/genética , Animais , Feminino , Linguado/genética , Masculino , Filogenia
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