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1.
Nucleic Acids Res ; 48(5): 2271-2286, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-31980822

RESUMO

The study of RNA expression is the fastest growing area of genomic research. However, despite the dramatic increase in the number of sequenced transcriptomes, we still do not have accurate estimates of the number and expression levels of non-coding RNA genes. Non-coding transcripts are often overlooked due to incomplete genome annotation. In this study, we use annotation-independent detection of RNA reads generated using a reverse transcriptase with low structure bias to identify non-coding RNA. Transcripts between 20 and 500 nucleotides were filtered and crosschecked with non-coding RNA annotations revealing 111 non-annotated non-coding RNAs expressed in different cell lines and tissues. Inspecting the sequence and structural features of these transcripts indicated that 60% of these transcripts correspond to new snoRNA and tRNA-like genes. The identified genes exhibited features of their respective families in terms of structure, expression, conservation and response to depletion of interacting proteins. Together, our data reveal a new group of RNA that are difficult to detect using standard gene prediction and RNA sequencing techniques, suggesting that reliance on actual gene annotation and sequencing techniques distorts the perceived architecture of the human transcriptome.


Assuntos
Anotação de Sequência Molecular/métodos , RNA Mensageiro/genética , RNA Nucleolar Pequeno/genética , RNA de Transferência/genética , RNA não Traduzido/genética , Transcriptoma , Animais , Pareamento de Bases , Sequência de Bases , Linhagem Celular Tumoral , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Conformação de Ácido Nucleico , Filogenia , RNA Mensageiro/classificação , RNA Mensageiro/metabolismo , RNA Nucleolar Pequeno/classificação , RNA Nucleolar Pequeno/metabolismo , RNA de Transferência/classificação , RNA de Transferência/metabolismo , RNA não Traduzido/classificação , RNA não Traduzido/metabolismo , Análise de Sequência de RNA , Sequenciamento Completo do Exoma
2.
Nat Struct Mol Biol ; 25(11): 1047-1058, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30374083

RESUMO

Transcriptome analysis reveals a strong positive correlation between human Schlafen family member 11 (SLFN11) expression and the sensitivity of tumor cells to DNA-damaging agents (DDAs). Here, we show that SLFN11 preferentially inhibits translation of the serine/threonine kinases ATR and ATM upon DDA treatment based on distinct codon usage without disrupting early DNA damage response signaling. Type II transfer RNAs (tRNAs), which include all serine and leucine tRNAs, are cleaved in a SLFN11-dependent manner in response to DDAs. Messenger RNAs encoded by genes with high TTA (Leu) codon usage, such as ATR, display utmost susceptibility to translational suppression by SLFN11. Specific attenuation of tRNA-Leu-TAA sufficed to ablate ATR protein expression and restore the DDA sensitivity of SLFN11-deficient cells. Our study uncovered a novel mechanism of codon-specific translational inhibition via SLFN11-dependent tRNA cleavage in the DNA damage response and supports the notion that SLFN11-deficient tumor cells can be resensitized to DDAs by targeting ATR or tRNA-Leu-TAA.


Assuntos
Morte Celular/fisiologia , Dano ao DNA , Proteínas Nucleares/metabolismo , RNA de Transferência/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/biossíntese , Proteínas Mutadas de Ataxia Telangiectasia/genética , Camptotecina/farmacologia , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Linhagem Celular Tumoral , Códon/genética , Células HEK293 , Humanos , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Biossíntese de Proteínas/efeitos dos fármacos , RNA Interferente Pequeno/genética , RNA de Transferência/classificação , RNA de Transferência/genética , RNA de Transferência de Leucina/genética , RNA de Transferência de Leucina/metabolismo , Inibidores da Topoisomerase I/farmacologia
3.
Bioinformatics ; 34(13): i237-i244, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29949978

RESUMO

Motivation: The convolutional neural network (CNN) has been applied to the classification problem of DNA sequences, with the additional purpose of motif discovery. The training of CNNs with distributed representations of four nucleotides has successfully derived position weight matrices on the learned kernels that corresponded to sequence motifs such as protein-binding sites. Results: We propose a novel application of CNNs to classification of pairwise alignments of sequences for accurate clustering of sequences and show the benefits of the CNN method of inputting pairwise alignments for clustering of non-coding RNA (ncRNA) sequences and for motif discovery. Classification of a pairwise alignment of two sequences into positive and negative classes corresponds to the clustering of the input sequences. After we combined the distributed representation of RNA nucleotides with the secondary-structure information specific to ncRNAs and furthermore with mapping profiles of next-generation sequence reads, the training of CNNs for classification of alignments of RNA sequences yielded accurate clustering in terms of ncRNA families and outperformed the existing clustering methods for ncRNA sequences. Several interesting sequence motifs and secondary-structure motifs known for the snoRNA family and specific to microRNA and tRNA families were identified. Availability and implementation: The source code of our CNN software in the deep-learning framework Chainer is available at http://www.dna.bio.keio.ac.jp/cnn/, and the dataset used for performance evaluation in this work is available at the same URL.


Assuntos
Biologia Computacional/métodos , Redes Neurais de Computação , RNA não Traduzido/metabolismo , Software , Adenocarcinoma/metabolismo , Sítios de Ligação , Análise por Conglomerados , Humanos , Masculino , MicroRNAs/química , MicroRNAs/classificação , MicroRNAs/metabolismo , Conformação de Ácido Nucleico , Neoplasias da Próstata/metabolismo , Ligação Proteica , RNA Nucleolar Pequeno/química , RNA Nucleolar Pequeno/classificação , RNA Nucleolar Pequeno/metabolismo , RNA de Transferência/química , RNA de Transferência/classificação , RNA de Transferência/metabolismo , RNA não Traduzido/química , RNA não Traduzido/classificação
4.
PLoS One ; 13(3): e0194672, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29584761

RESUMO

In the present study, we report five complete and one nearly complete mitochondrial genomes of the Pyraloidea including the first representatives from the Pyralinae (Pyralidae) and Glaphyriinae (Crambidae). We also conduct a comparative analysis of mitogenomic features of this group. Our results show that Pyraloidea mitogenomes evolved under a common trend found in lepidopteran mitogenomes and share several typical genomic characters. The extra conserved blocks are identified in the Pyraloidea control region, and diverse missing codons formed another unique trait within Pyraloidea mitogenome. Furthermore, we reconstruct the mitogenomic phylogeny of Pyraloidea and confirm the phylogenetic position of Pyralinae and Glaphyriinae within the Pyraloidea using BI and ML method based on multiple mitochondrial datasets.


Assuntos
Genoma Mitocondrial , Mariposas/genética , Animais , Códon , DNA/química , DNA/isolamento & purificação , DNA/metabolismo , Bases de Dados Genéticas , Mariposas/classificação , Filogenia , RNA Ribossômico/classificação , RNA Ribossômico/genética , RNA de Transferência/classificação , RNA de Transferência/genética , Análise de Sequência de DNA
5.
Nucleic Acids Res ; 46(3): e15, 2018 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-29155959

RESUMO

Small non-coding RNAs (sncRNAs) are highly abundant molecules that regulate essential cellular processes and are classified according to sequence and structure. Here we argue that read profiles from size-selected RNA sequencing capture the post-transcriptional processing specific to each RNA family, thereby providing functional information independently of sequence and structure. We developed SeRPeNT, a new computational method that exploits reproducibility across replicates and uses dynamic time-warping and density-based clustering algorithms to identify, characterize and compare sncRNAs by harnessing the power of read profiles. We applied SeRPeNT to: (i) generate an extended human annotation with 671 new sncRNAs from known classes and 131 from new potential classes, (ii) show pervasive differential processing of sncRNAs between cell compartments and (iii) predict new molecules with miRNA-like behaviour from snoRNA, tRNA and long non-coding RNA precursors, potentially dependent on the miRNA biogenesis pathway. Furthermore, we validated experimentally four predicted novel non-coding RNAs: a miRNA, a snoRNA-derived miRNA, a processed tRNA and a new uncharacterized sncRNA. SeRPeNT facilitates fast and accurate discovery and characterization of sncRNAs at an unprecedented scale. SeRPeNT code is available under the MIT license at https://github.com/comprna/SeRPeNT.


Assuntos
Algoritmos , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Nucleolar Pequeno/genética , Pequeno RNA não Traduzido/genética , RNA de Transferência/genética , Sequência de Bases , Análise por Conglomerados , Perfil Genético , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Internet , MicroRNAs/classificação , Anotação de Sequência Molecular , RNA Longo não Codificante/classificação , RNA Nucleolar Pequeno/classificação , Pequeno RNA não Traduzido/classificação , RNA de Transferência/classificação , Reprodutibilidade dos Testes , Software
6.
Gigascience ; 7(2)2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29267854

RESUMO

Background: Milu, also known as Père David's deer (Elaphurus davidianus), was widely distributed in East Asia but recently experienced a severe bottleneck. Only 18 survived by the end of the 19th century, and the current population of 4500 individuals was propagated from just 11 kept by the 11th British Duke of Bedford. This species is known for its distinguishable appearance, the driving force behind which is still a mystery. To aid efforts to explore these phenomena, we constructed a draft genome of the species. Findings: In total, we generated 321.86 gigabases (Gb) of raw DNA sequence from whole-genome sequencing of a male milu deer using an Illumina HiSeq 2000 platform. Assembly yielded a final genome with a scaffold N50 size of 3.03 megabases (Mb) and a total length of 2.52 Gb. Moreover, we identified 20 125 protein-coding genes and 988.1 Mb of repetitive sequences. In addition, homology-based searches detected 280 rRNA, 1335 miRNA, 1441 snRNA, and 893 tRNA sequences in the milu genome. The divergence time between E. davidianus and Bos taurus was estimated to be about 28.20 million years ago (Mya). We identified 167 species-specific genes and 293 expanded gene families in the milu lineage. Conclusions: We report the first reference genome of milu, which will provide a valuable resource for studying the species' demographic history of severe bottleneck and the genetic mechanism(s) of special phenotypic evolution.


Assuntos
Evolução Biológica , Mapeamento Cromossômico/métodos , Cervos/genética , Genoma , Sequenciamento de Nucleotídeos em Larga Escala , Animais , Bovinos , Cervos/classificação , Masculino , MicroRNAs/classificação , MicroRNAs/genética , Fases de Leitura Aberta , Filogenia , Proteínas/classificação , Proteínas/genética , RNA Ribossômico/classificação , RNA Ribossômico/genética , RNA Nuclear Pequeno/classificação , RNA Nuclear Pequeno/genética , RNA de Transferência/classificação , RNA de Transferência/genética , Sequenciamento Completo do Genoma
7.
RNA Biol ; 15(1): 95-103, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-29099311

RESUMO

Small RNAs (sRNAs) in bacteria have emerged as key players in transcriptional and post-transcriptional regulation of gene expression. Here, we present a statistical analysis of different sequence- and structure-related features of bacterial sRNAs to identify the descriptors that could discriminate sRNAs from other bacterial RNAs. We investigated a comprehensive and heterogeneous collection of 816 sRNAs, identified by northern blotting across 33 bacterial species and compared their various features with other classes of bacterial RNAs, such as tRNAs, rRNAs and mRNAs. We observed that sRNAs differed significantly from the rest with respect to G+C composition, normalized minimum free energy of folding, motif frequency and several RNA-folding parameters like base-pairing propensity, Shannon entropy and base-pair distance. Based on the selected features, we developed a predictive model using Random Forests (RF) method to classify the above four classes of RNAs. Our model displayed an overall predictive accuracy of 89.5%. These findings would help to differentiate bacterial sRNAs from other RNAs and further promote prediction of novel sRNAs in different bacterial species.


Assuntos
RNA Mensageiro/genética , RNA Ribossômico/genética , Pequeno RNA não Traduzido/genética , RNA de Transferência/genética , Bactérias/genética , Composição de Bases/genética , Pareamento de Bases , Regulação Bacteriana da Expressão Gênica , RNA Bacteriano/classificação , RNA Bacteriano/genética , RNA Mensageiro/classificação , RNA Ribossômico/classificação , Pequeno RNA não Traduzido/classificação , RNA de Transferência/classificação
8.
Mol Phylogenet Evol ; 115: 58-61, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28754240

RESUMO

Pseudemydura umbrina is one of the most endangered turtle species in the world, and the imperative for its conservation is its distinctive morphology and relict status among the Chelidae. We use Illumina sequencing to obtain the complete mitogenome for resolving its uncertain phylogenetic position. A novel nuclear paralogue confounded the assembly, and resolution of the authentic mitogenome required further Sanger sequencing. The P. umbrina mitogenome is 16,414bp comprising 37 genes organized in a conserved pattern for other vertebrates. The nuclear paralogue is 547bp, 97.8% identity to the corresponding mitochondrial sequence. Particular features of the mitogenome include an nd3 174+1A frameshift, loss of DHC loop in tRNASer (AGN), and a light-strand replication initiation site in Wancy region that extends into an adjacent tRNA gene. Phylogenetic analysis showed that P. umbrina is the monotypic sister lineage to the remaining Australasian Chelidae, a lineage probably dating back to the Cretaceous.


Assuntos
Genoma Mitocondrial , Tartarugas/classificação , Animais , Espécies em Perigo de Extinção , Filogenia , RNA de Transferência/classificação , RNA de Transferência/genética , RNA de Transferência/metabolismo , Tartarugas/genética
9.
Artif Intell Med ; 83: 82-90, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28245947

RESUMO

Selective ensemble learning is a technique that selects a subset of diverse and accurate basic models in order to generate stronger generalization ability. In this paper, we proposed a novel learning algorithm that is based on parallel optimization and hierarchical selection (PTHS). Our novel feature selection method is based on maximize the sum of relevance and distance (MSRD) for solving the problem of high dimensionality. Specifically, we have a PTHS algorithm that employs parallel optimization and candidate model pruning based on k-means and a hierarchical selection framework. We combine the prediction result of each basic model by majority voting, which employs the divide-and-conquer strategy to save computing time. In addition, the PT algorithm is capable to transform a multi-class problem into a binary classification problem, and thereby allowing our ensemble model to address multi-class problems. Empirical study shows that MSRD is efficient in solving the high dimensionality problem, and PTHS exhibits better performance than the other existing classification algorithms. Most importantly, our classifier achieved high-level performance on several bioinformatics problems (e.g. tRNA identification, and protein-protein interaction prediction, etc.), demonstrating efficiency and robustness.


Assuntos
Biologia Computacional/métodos , Mineração de Dados/métodos , Aprendizado de Máquina , Proteínas/classificação , RNA de Transferência/classificação , Área Sob a Curva , Bases de Dados Genéticas , Mapas de Interação de Proteínas , Proteínas/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , Curva ROC , Reprodutibilidade dos Testes
10.
Mol Phylogenet Evol ; 106: 158-163, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27693570

RESUMO

The gene duplication in mitochondrial DNA (mtDNA) has been reported in diverse bird taxa so far. Although many phylogenetic and population genetic analyses of cranes were carried out based on mtDNA diversity, whether mtDNA contains duplicated regions is unknown. To address the presence or absence of gene duplication in cranes and investigate the molecular evolutionary features of crane mtDNA, we analyzed the gene organization and the molecular phylogeny of mtDNA from 13 crane species. We found that the mtDNA in 13 crane species shared a tandem duplicated region, which consists of duplicated sequence sets including cytochrome b (Cytb), NADH6, control region (CR) and three genes of tRNA. The gene order in the duplicated region was identical among all the 13 crane species, and the nucleotide sequences found within each individual showed high similarities. In addition, phylogenetic trees based on homologous sequences of CR and Cytb indicated the possibility of concerted evolution among the duplicated genes. The results suggested that the duplication event occurred in the common ancestor of crane species or some older ancestors.


Assuntos
Aves/genética , DNA Mitocondrial/genética , Evolução Molecular , Animais , Aves/classificação , Citocromos b/classificação , Citocromos b/genética , DNA/química , DNA/isolamento & purificação , DNA/metabolismo , DNA Mitocondrial/classificação , DNA Mitocondrial/metabolismo , Duplicação Gênica , Filogenia , RNA de Transferência/classificação , RNA de Transferência/genética , Análise de Sequência de DNA
11.
Sci Rep ; 6: 39153, 2016 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-27974854

RESUMO

The complete mitochondrial genome (mitogenome) of Leucoma salicis (Lepidoptera: Lymantriidae) was sequenced and annotated. It is a circular molecule of 15,334 bp, containing the 37 genes usually present in insect mitogenomes. All protein-coding genes (PCGs) are initiated by ATN codons, other than cox1, which is initiated by CGA. Three of the 13 PCGs had an incomplete termination codon, T or TA, while the others terminated with TAA. The relative synonymous codon usage of the 13 protein-coding genes (PCGs) was consistent with those of published lepidopteran sequences. All tRNA genes had typical clover-leaf secondary structures, except for the tRNASer (AGN), in which the dihydrouridine (DHU) arm could not form a stable stem-loop structure. The A + T-rich region of 325 bp had several distinctive features, including the motif 'ATAGA' followed by an 18 bp poly-T stretch, a microsatellite-like (AT)7 element, and an 11-bp poly-A present immediately upstream of tRNAMet. Relationships among 32 insect species were determined using Maximum Likelihood (ML), Neighbor Joining (NJ) and Bayesian Inference (BI) phylogenetic methods. These analyses confirm that L. salicis belongs to the Lymantriidae; and that Lymantriidae is a member of Noctuoidea, and is a sister taxon to Erebidae, Nolidae and Noctuidae, most closely related to Erebidae.


Assuntos
Genoma Mitocondrial , Lepidópteros/genética , Mariposas/genética , Animais , Sequência de Bases , Teorema de Bayes , Códon de Terminação , DNA Mitocondrial/química , DNA Mitocondrial/isolamento & purificação , DNA Mitocondrial/metabolismo , Lepidópteros/classificação , Funções Verossimilhança , Mariposas/classificação , Conformação de Ácido Nucleico , Fases de Leitura Aberta/genética , Filogenia , RNA Ribossômico/classificação , RNA Ribossômico/genética , RNA de Transferência/química , RNA de Transferência/classificação , RNA de Transferência/genética , Análise de Sequência de DNA
12.
Mol Phylogenet Evol ; 104: 99-111, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27497607

RESUMO

The Coleoptera (beetles) exhibits tremendous morphological, ecological, and behavioral diversity. To better understand the phylogenetics and evolution of beetles, we sequenced three complete mitogenomes from two families (Cleridae and Meloidae), which share conserved mitogenomic features with other completely sequenced beetles. We assessed the influence of six datasets and three inference methods on topology and nodal support within the Coleoptera. We found that both Bayesian inference and maximum likelihood with homogeneous-site models were greatly affected by nucleotide compositional heterogeneity, while the heterogeneous-site mixture model in PhyloBayes could provide better phylogenetic signals for the Coleoptera. The amino acid dataset generated more reliable tree topology at the higher taxonomic levels (i.e. suborders and series), where the inclusion of rRNA genes and the third positions of protein-coding genes improved phylogenetic inference at the superfamily level, especially under a heterogeneous-site model. We recovered the suborder relationships as (Archostemata+Adephaga)+(Myxophaga+Polyphaga). The series relationships within Polyphaga were recovered as (Scirtiformia+(Elateriformia+((Bostrichiformia+Scarabaeiformia+Staphyliniformia)+Cucujiformia))). All superfamilies within Cucujiformia were recovered as monophyletic. We obtained a cucujiform phylogeny of (Cleroidea+(Coccinelloidea+((Lymexyloidea+Tenebrionoidea)+(Cucujoidea+(Chrysomeloidea+Curculionoidea))))). This study showed that although tree topologies were sensitive to data types and inference methods, mitogenomic data could provide useful information for resolving the Coleoptera phylogeny at various taxonomic levels by using suitable datasets and heterogeneous-site models.


Assuntos
Genoma Mitocondrial , Animais , Teorema de Bayes , Besouros/classificação , Besouros/genética , DNA/química , DNA/isolamento & purificação , DNA/metabolismo , DNA Mitocondrial/classificação , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Filogenia , RNA Ribossômico/classificação , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , RNA de Transferência/classificação , RNA de Transferência/genética , RNA de Transferência/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNA
13.
Mol Phylogenet Evol ; 104: 14-20, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27444707

RESUMO

The phylogeny of tits has been studied using various molecular markers, but their phylogenetic relationships remain controversial. To further investigate their taxonomic status and phylogenetic relationships, the entire mitochondrial genomes (mitogenomes) and five nuclear segments were sequenced from 10 species of tits and two outgroups (Sylviparus modestus and Remiz consobrinus), followed by the comparison of mitogenomic characteristics and reconstruction of phylogenetic relationship based on the different datasets. The results revealed the following: the mitogenomes of 10 ingroup tits, each 16,758-16,799bp in length, displayed typical mitogenome organization and the gene order found in most previously determined Passeriformes mitogenomes; close relationships existed between Parus major and P. monticolus, between P. montanus and P. palustris, and between P. ater and P. venustulus; and Pseudopodoces humilis was a sister group to P. spilonotus, P. cyanus, or the clade containing P. major and P. monticolus.


Assuntos
Passeriformes/classificação , Animais , DNA/química , DNA/isolamento & purificação , DNA/metabolismo , Genoma Mitocondrial , Passeriformes/genética , Filogenia , RNA Ribossômico/classificação , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , RNA de Transferência/classificação , RNA de Transferência/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNA
14.
RNA Biol ; 13(9): 810-9, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27322343

RESUMO

Transfer RNAs (tRNAs) have been important in shaping biomolecular evolution. Initiator tRNAs (tRNAi), a special class of tRNAs, carry methionine (or its derivative, formyl-methionine) to ribosomes to start an enormously energy consuming but a highly regulated process of protein synthesis. The processes of tRNAi evolution, and selection of methionine as the universal initiating amino acid remain an enigmatic problem. We constructed phylogenetic trees using the whole sequence, the acceptor-TψC arm ('minihelix'), and the anticodon-dihydrouridine arm regions of tRNAi from 158 species belonging to all 3 domains of life. All the trees distinctly assembled into 3 domains of life. Large trees, generated using data for all the tRNAs of a vast number of species, fail to reveal the major evolutionary events and identity of the probable elongator tRNA sequences that could be ancestor of tRNAi. Therefore, we constructed trees using the minihelix or the whole sequence of species specific tRNAs, and iterated our analysis on 50 eubacterial species. We identified tRNA(Pro), tRNA(Glu), or tRNA(Thr) (but surprisingly not elongator tRNA(Met)) as probable ancestors of tRNAi. We then determined the factors imposing selection of methionine as the initiating amino acid. Overall frequency of occurrence of methionine, whose metabolic cost of synthesis is the highest among all amino acids, remains almost unchanged across the 3 domains of life. Our correlation analysis shows that its high metabolic cost is independent of many physicochemical properties of the side chain. Our results indicate that selection of methionine, as the initiating amino acid was possibly a consequence of the evolution of one-carbon metabolism, which plays an important role in regulating translation initiation.


Assuntos
Evolução Molecular , Iniciação Traducional da Cadeia Peptídica , RNA de Transferência de Metionina/genética , RNA de Transferência/genética , Sequência de Bases , Sequência Conservada , Modelos Moleculares , Conformação de Ácido Nucleico , Filogenia , RNA de Transferência/química , RNA de Transferência/classificação , RNA de Transferência de Metionina/química
15.
PLoS One ; 11(6): e0158129, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27336480

RESUMO

The mitochondrion is the power plant of the eukaryotic cell, and tRNAs are the fundamental components of its translational machinery. In the present paper, the evolution of mitochondrial tRNAs was investigated in the Cetacea, a clade of Cetartiodactyla that retuned to water and thus had to adapt its metabolism to a different medium than that of its mainland ancestors. Our analysis focussed on identifying the factors that influenced the evolution of Cetacea tRNA double-helix elements, which play a pivotal role in the formation of the secondary and tertiary structures of each tRNA and consequently manipulate the whole translation machinery of the mitochondrion. Our analyses showed that the substitution pathways in the stems of different tRNAs were influenced by various factors, determining a molecular evolution that was unique to each of the 22 tRNAs. Our data suggested that the composition, AT-skew, and GC-skew of the tRNA stems were the main factors influencing the substitution process. In particular, the range of variation and the fluctuation of these parameters affected the fate of single tRNAs. Strong heterogeneity was observed among the different species of Cetacea. Finally, it appears that the evolution of mitochondrial tRNAs was also shaped by the environments in which the Cetacean taxa differentiated. This latter effect was particularly evident in toothed whales that either live in freshwater or are deep divers.


Assuntos
Adaptação Biológica , Cetáceos/genética , Evolução Molecular , Genes Mitocondriais , RNA de Transferência/genética , Animais , Cetáceos/classificação , Códon , Biologia Computacional/métodos , DNA Mitocondrial , Perfilação da Expressão Gênica , Variação Genética , Genoma Mitocondrial , Conformação de Ácido Nucleico , Filogenia , RNA de Transferência/química , RNA de Transferência/classificação , Análise de Sequência de DNA , Especificidade da Espécie
16.
Oncotarget ; 6(28): 24797-822, 2015 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-26325506

RESUMO

We analyzed transcriptomic data from 452 healthy men and women representing five different human populations and two races, and, 311 breast cancer samples from The Cancer Genome Atlas. Our studies revealed numerous constitutive, distinct fragments with overlapping sequences and quantized lengths that persist across dozens of individuals and arise from the genomic loci of all nuclear and mitochondrial human transfer RNAs (tRNAs). Surprisingly, we discovered that the tRNA fragments' length, starting and ending points, and relative abundance depend on gender, population, race and also on amino acid identity, anticodon, genomic locus, tissue, disease, and disease subtype. Moreover, the length distribution of mitochondrially-encoded tRNAs differs from that of nuclearly-encoded tRNAs, and the specifics of these distributions depend on tissue. Notably, tRNA fragments from the same anticodon do not have correlated abundances. We also report on a novel category of tRNA fragments that significantly contribute to the differences we observe across tissues, genders, populations, and races: these fragments, referred to as i-tRFs, are abundant in human tissues, wholly internal to the respective mature tRNA, and can straddle the anticodon. HITS-CLIP data analysis revealed that tRNA fragments are loaded on Argonaute in a cell-dependent manner, suggesting cell-dependent functional roles through the RNA interference pathway. We validated experimentally two i-tRF molecules: the first was found in 21 of 22 tested breast tumor and adjacent normal samples and was differentially abundant between health and disease whereas the second was found in all eight tested breast cancer cell lines.


Assuntos
Regulação da Expressão Gênica , RNA de Transferência/genética , RNA/genética , Transcriptoma/genética , Anticódon/genética , Sequência de Bases , Neoplasias da Mama/genética , Linhagem Celular , Linhagem Celular Tumoral , Análise por Conglomerados , Feminino , Variação Genética , Humanos , Células MCF-7 , Masculino , Modelos Genéticos , Dados de Sequência Molecular , Conformação de Ácido Nucleico , RNA/química , RNA Mitocondrial , RNA de Transferência/química , RNA de Transferência/classificação
17.
Mol Cell ; 58(3): 393-405, 2015 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-25891076

RESUMO

During ribosomal and transfer RNA maturation, external transcribed spacer (ETS) and internal transcribed spacer (ITS) sequences are excised and, as non-functional by-products, are rapidly degraded. However, we report that the 3'ETS of the glyW-cysT-leuZ polycistronic tRNA precursor is highly and specifically enriched by co-purification with at least two different small regulatory RNAs (sRNAs), RyhB and RybB. Both sRNAs are shown to base pair with the same region in the 3'ETS of leuZ (3'ETS(leuZ)). Disrupting the pairing by mutating 3'ETS(leuZ) strongly increased the activity of sRNAs, even under non-inducing conditions. Our results indicate that 3'ETS(leuZ) prevents sRNA-dependent remodeling of tricarboxylic acid (TCA) cycle fluxes and decreases antibiotic sensitivity when sRNAs are transcriptionally repressed. This suggests that 3'ETS(leuZ) functions as a sponge to absorb transcriptional noise from repressed sRNAs. Additional data showing RybB and MicF sRNAs are co-purified with ITS(metZ-metW) and ITS(metW-metV) strongly suggest a wide distribution of this phenomenon.


Assuntos
Precursores de RNA/genética , RNA Bacteriano/genética , Pequeno RNA não Traduzido/genética , RNA de Transferência/genética , Transcrição Genética , Sequência de Bases , Northern Blotting , Western Blotting , Carboidratos Epimerases/genética , Carboidratos Epimerases/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Modelos Genéticos , Modelos Moleculares , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Precursores de RNA/química , Precursores de RNA/classificação , RNA Bacteriano/química , Pequeno RNA não Traduzido/química , RNA de Transferência/química , RNA de Transferência/classificação , Análise de Sequência de RNA , Homologia de Sequência do Ácido Nucleico , Fator sigma/genética , Fator sigma/metabolismo
18.
J Biomol Struct Dyn ; 33(12): 2721-37, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25692737

RESUMO

tRNAs are widely believed to segregate into two classes, I and II. Computational analysis of eukaryotic tRNA entries in Genomic tRNA Database, however, leads to new, albeit paradoxical, presence of more than a thousand class-I tRNAs with uncharacteristic long variable arms (V-arms), like in class-II. Out of 62,202 tRNAs from 69 eukaryotes, as many as 1431 class-I tRNAs have these novel extended V-arms, and we refer to them as paradoxical tRNAs (pxtRNAs). A great majority of these 1431 pxtRNA genes are located in intergenic regions, about 18% embedded in introns of genes or ESTs, and just one in 3'UTR. A check on the conservations of 2D and 3D base pairs for each position of these pxtRNAs reveals a few variations, but they seem to have almost all the known features (already known identity and conserved elements of tRNA). Analyses of the A-Box and B-Box of these pxtRNA genes in eukaryotes display salient deviations from the previously annotated conserved features of the standard promoters, whereas the transcription termination signals are just canonical and non-canonical runs of thymidine, similar to the ones in standard tRNA genes. There is just one such pxtRNA(ProAGG) gene in the entire human genome, and the availability of data allows epigenetic analysis of this human pxtRNA(ProAGG) in three different cell lines, H1 hESC, K562, and NHEK, to assess the level of its expression. Histone acetylation and methylation of this lone pxtRNA(ProAGG) gene in human differ from that of the nine standard human tRNA(ProAGG) genes. The V-arm nucleotide sequences and their secondary structures in pxtRNA differ from that of class-II tRNA. Considering these differences, hypotheses of alternative splicing, non-canonical intron and gene transfer are examined to partially improve the Cove scores of these pxtRNAs and to critically question their antecedence and novelty.


Assuntos
DNA Intergênico/genética , Eucariotos/genética , Íntrons/genética , RNA de Transferência/genética , Sequência de Bases , Linhagem Celular , Simulação por Computador , Epigênese Genética , Eucariotos/classificação , Evolução Molecular , Regulação da Expressão Gênica , Variação Genética , Humanos , Células K562 , Modelos Moleculares , Conformação de Ácido Nucleico , Filogenia , Regiões Promotoras Genéticas/genética , RNA de Transferência/química , RNA de Transferência/classificação , Transcrição Genética
19.
Front Biosci (Landmark Ed) ; 19: 1117-50, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24896340

RESUMO

This study tracks the rise, evolution and post-evolution of the genetic information system through emergence of life. The major stages traversed include prebiotic synthesis, functional RNA selection by metabolite, RNA World, peptidated RNA world, co-evolution of genetic code and amino acid biosynthesis, last universal common ancestor, Darwinian evolution and synthetic life.


Assuntos
Evolução Molecular , Código Genético/genética , Origem da Vida , RNA/genética , Seleção Genética , Animais , Evolução Biológica , Humanos , Filogenia , RNA/metabolismo , RNA de Transferência/classificação , RNA de Transferência/genética
20.
Gene ; 530(2): 229-35, 2013 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-23973725

RESUMO

The sequence of the chloroplast genome, which is inherited maternally, contains useful information for many scientific fields such as plant systematics, biogeography and biotechnology because its characteristics are highly conserved among species. There is an increase in chloroplast genomes of angiosperms that have been sequenced in recent years. In this study, the nucleotide sequence of the chloroplast genome (cpDNA) of Veratrum patulum Loes. (Melanthiaceae, Liliales) was analyzed completely. The circular double-stranded DNA of 153,699 bp consists of two inverted repeat (IR) regions of 26,360 bp each, a large single copy of 83,372 bp, and a small single copy of 17,607 bp. This plastome contains 81 protein-coding genes, 30 distinct tRNA and four genes of rRNA. In addition, there are six hypothetical coding regions (ycf1, ycf2, ycf3, ycf4, ycf15 and ycf68) and two open reading frames (ORF42 and ORF56), which are also found in the chloroplast genomes of the other species. The gene orders and gene contents of the V. patulum plastid genome are similar to that of Smilax china, Lilium longiflorum and Alstroemeria aurea, members of the Smilacaceae, Liliaceae and Alstroemeriaceae (Liliales), respectively. However, the loss rps16 exon 2 in V. patulum results in the difference in the large single copy regions in comparison with other species. The base substitution rate is quite similar among genes of these species. Additionally, the base substitution rate of inverted repeat region was smaller than that of single copy regions in all observed species of Liliales. The IR regions were expanded to trnH_GUG in V. patulum, a part of rps19 in L. longiflorum and A. aurea, and whole sequence of rps19 in S. china. Furthermore, the IGS lengths of rbcL-accD-psaI region were variable among Liliales species, suggesting that this region might be a hotspot of indel events and the informative site for phylogenetic studies in Liliales. In general, the whole chloroplast genome of V. patulum, a potential medicinal plant, will contribute to research on the genetic applications of this genus.


Assuntos
Cloroplastos/genética , Genoma de Cloroplastos , Genômica , Filogenia , RNA de Plantas/genética , Veratrum/genética , Cloroplastos/classificação , Mapeamento Cromossômico , DNA Circular , Sequências Repetidas Invertidas , Liliaceae/classificação , Liliaceae/genética , RNA de Plantas/classificação , RNA Ribossômico/classificação , RNA Ribossômico/genética , RNA de Transferência/classificação , RNA de Transferência/genética , Smilacaceae/classificação , Smilacaceae/genética , Veratrum/classificação
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