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2.
BMC Bioinformatics ; 20(Suppl 24): 596, 2019 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-31861975

RESUMO

BACKGROUND: Adenosine-to-inosine RNA editing can markedly diversify the transcriptome, leading to a variety of critical molecular and biological processes in mammals. Over the past several years, researchers have developed several new pipelines and software packages to identify RNA editing sites with a focus on downstream statistical analysis and functional interpretation. RESULTS: Here, we developed a user-friendly public webserver named MIRIA that integrates statistics and visualization techniques to facilitate the comprehensive analysis of RNA editing sites data identified by the pipelines and software packages. MIRIA is unique in that provides several analytical functions, including RNA editing type statistics, genomic feature annotations, editing level statistics, genome-wide distribution of RNA editing sites, tissue-specific analysis and conservation analysis. We collected high-throughput RNA sequencing (RNA-seq) data from eight tissues across seven species as the experimental data for MIRIA and constructed an example result page. CONCLUSION: MIRIA provides both visualization and analysis of mammal RNA editing data for experimental biologists who are interested in revealing the functions of RNA editing sites. MIRIA is freely available at https://mammal.deepomics.org.


Assuntos
Mamíferos , Edição de RNA , Análise de Sequência de RNA , Transcriptoma , Animais , Genoma , Genômica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Mamíferos/genética , RNA/genética , Análise de Sequência de RNA/métodos
3.
Biochemistry (Mosc) ; 84(8): 896-904, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31522671

RESUMO

RNA editing by adenosine deaminases of the ADAR family attracts a growing interest of researchers, both zoologists studying ecological and evolutionary plasticity of invertebrates and medical biochemists focusing on the mechanisms of cancer and other human diseases. These enzymes deaminate adenosine residues in the double-stranded (ds) regions of RNA with the formation of inosine. As a result, some RNAs change their three-dimensional structure and functions. Adenosine-to-inosine editing in the mRNA coding sequences may cause amino acid substitutions in the encoded proteins. Here, we reviewed current concepts on the functions of two active ADAR isoforms identified in mammals (including humans). The ADAR1 protein, which acts non-specifically on extended dsRNA regions, is capable of immunosuppression via inactivation of the dsRNA interactions with specific sensors inducing the cell immunity. Expression of a specific ADAR1 splicing variant is regulated by the type I interferons by the negative feedback mechanism. It was shown that immunosuppressing effects of ADAR1 facilitate progression of some types of cancer. On the other hand, changes in the amino acid sequences resulting from the mRNA editing by the ADAR enzymes can result in the formation of neoantigens that can activate the antitumor immunity. The ADAR2 isoform acts on RNA more selectively; its function is associated with the editing of mRNA coding regions and can lead to the amino acid substitutions, in particular, those essential for the proper functioning of some neurotransmitter receptors in the central nervous system.


Assuntos
Adenosina Desaminase/metabolismo , Carcinogênese/metabolismo , Plasticidade Neuronal/fisiologia , Edição de RNA/fisiologia , Proteínas de Ligação a RNA/metabolismo , Adenosina Desaminase/imunologia , Sequência de Aminoácidos , Animais , Senescência Celular/fisiologia , Humanos , Inosina/metabolismo , Interferon Tipo I/metabolismo , Proteoma/metabolismo , RNA de Cadeia Dupla/metabolismo , Proteínas de Ligação a RNA/imunologia
4.
Genes (Basel) ; 10(9)2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31509970

RESUMO

The multiple organellar RNA editing factors (MORF) gene family plays a key role in organelle RNA editing in flowering plants. MORF genes expressions are also affected by abiotic stress. Although seven OsMORF genes have been identified in rice, few reports have been published on their expression patterns in different tissues and under abiotic stress, and OsMORF-OsMORF interactions. In this study, we analyzed the gene structure of OsMORF family genes. The MORF family members were divided into six subgroups in different plants based on phylogenetic analysis. Seven OsMORF genes were highly expressed in leaves. Six and seven OsMORF genes expressions were affected by cold and salt stresses, respectively. OsMORF-OsMORF interaction analysis indicated that OsMORF1, OsMORF8a, and OsMORF8b could each interact with themselves to form homomers. Moreover, five OsMORF proteins were shown to be able to interact with each other, such as OsMORF8a and OsMORF8b interacting with OsMORF1 and OsMORF2b, respectively, to form heteromers. These results provide information for further study of OsMORF gene function.


Assuntos
Oryza/genética , Proteínas de Plantas/genética , Proteínas de Ligação a RNA/genética , Resposta ao Choque Frio , Família Multigênica , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Ligação Proteica , Edição de RNA , Proteínas de Ligação a RNA/metabolismo , Estresse Salino
5.
Nat Rev Drug Discov ; 18(9): 667, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31477858
6.
Nat Neurosci ; 22(9): 1402-1412, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31455887

RESUMO

RNA editing critically regulates neurodevelopment and normal neuronal function. The global landscape of RNA editing was surveyed across 364 schizophrenia cases and 383 control postmortem brain samples from the CommonMind Consortium, comprising two regions: dorsolateral prefrontal cortex and anterior cingulate cortex. In schizophrenia, RNA editing sites in genes encoding AMPA-type glutamate receptors and postsynaptic density proteins were less edited, whereas those encoding translation initiation machinery were edited more. These sites replicate between brain regions, map to 3'-untranslated regions and intronic regions, share common sequence motifs and overlap with binding sites for RNA-binding proteins crucial for neurodevelopment. These findings cross-validate in hundreds of non-overlapping dorsolateral prefrontal cortex samples. Furthermore, ~30% of RNA editing sites associate with cis-regulatory variants (editing quantitative trait loci or edQTLs). Fine-mapping edQTLs with schizophrenia risk loci revealed co-localization of eleven edQTLs with six loci. The findings demonstrate widespread altered RNA editing in schizophrenia and its genetic regulation, and suggest a causal and mechanistic role of RNA editing in schizophrenia neuropathology.


Assuntos
Córtex Cerebral/metabolismo , Edição de RNA/genética , Esquizofrenia/genética , Córtex Cerebral/fisiopatologia , Estudos de Coortes , Estudo de Associação Genômica Ampla , Humanos , Locos de Características Quantitativas/genética
7.
Int J Mol Sci ; 20(17)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443555

RESUMO

Carnivorous plants have the ability to capture and digest small animals as a source of additional nutrients, which allows them to grow in nutrient-poor habitats. Here we report the complete sequences of the plastid genomes of two carnivorous plants of the order Caryophyllales, Drosera rotundifolia and Nepenthes × ventrata. The plastome of D. rotundifolia is repeat-rich and highly rearranged. It lacks NAD(P)H dehydrogenase genes, as well as ycf1 and ycf2 genes, and three essential tRNA genes. Intron losses are observed in some protein-coding and tRNA genes along with a pronounced reduction of RNA editing sites. Only six editing sites were identified by RNA-seq in D. rotundifolia plastid genome and at most conserved editing sites the conserved amino acids are already encoded at the DNA level. In contrast, the N. × ventrata plastome has a typical structure and gene content, except for pseudogenization of the ccsA gene. N. × ventrata and D. rotundifolia could represent different stages of evolution of the plastid genomes of carnivorous plants, resembling events observed in parasitic plants in the course of the switch from autotrophy to a heterotrophic lifestyle.


Assuntos
Evolução Biológica , Drosera/genética , Genomas de Plastídeos , Genômica , Biologia Computacional/métodos , Drosera/parasitologia , Duplicação Gênica , Rearranjo Gênico , Genes de Plantas , Genômica/métodos , Edição de RNA
8.
PLoS Genet ; 15(8): e1008305, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31374076

RESUMO

C-to-U editing is an important event in post-transcriptional RNA processing, which converts a specific cytidine (C)-to-uridine (U) in transcripts of mitochondria and plastids. Typically, the pentatricopeptide repeat (PPR) protein, which specifies the target C residue by binding to its upstream sequence, is involved in the editing of one or a few sites. Here we report a novel PPR-DYW protein EMP21 that is associated with editing of 81 sites in maize. EMP21 is localized in mitochondria and loss of the EMP21 function severely inhibits the embryogenesis and endosperm development in maize. From a scan of 35 mitochondrial transcripts produced by the Emp21 loss-of-function mutant, the C-to-U editing was found to be abolished at five sites (nad7-77, atp1-1292, atp8-437, nad3-275 and rps4-870), while reduced at 76 sites in 21 transcripts. In most cases, the failure to editing resulted in the translation of an incorrect residue. In consequence, the mutant became deficient with respect to the assembly and activity of mitochondrial complexes I and V. As six of the decreased editing sites in emp21 overlap with the affected editing sites in emp5-1, and the editing efficiency at rpl16-458 showed a substantial reduction in the emp21-1 emp5-4 double mutant compared with the emp21-1 and emp5-4 single mutants, we explored their interaction. A yeast two hybrid assay suggested that EMP21 does not interact with EMP5, but both EMP21 and EMP5 interact with ZmMORF8. Together, these results indicate that EMP21 is a novel PPR-DYW protein required for the editing of ~17% of mitochondrial target Cs, and the editing process may involve an interaction between EMP21 and ZmMORF8 (and probably other proteins).


Assuntos
Proteínas de Plantas/metabolismo , Edição de RNA , RNA Mitocondrial/metabolismo , Proteínas de Ligação a RNA/metabolismo , Zea mays/fisiologia , Complexo I de Transporte de Elétrons/metabolismo , Desenvolvimento Embrionário/genética , Endosperma/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Mutação com Perda de Função , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Domínios Proteicos/genética , Proteínas de Ligação a RNA/genética
9.
Nat Rev Genet ; 20(10): 563, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31388142
10.
BMC Evol Biol ; 19(1): 149, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337330

RESUMO

BACKGROUND: Adenosine deaminase enzymes of the ADAR family are conserved in metazoans. They convert adenine into inosine in dsRNAs and thus alter both structural properties and the coding potential of their substrates. Acting on exogenous dsRNAs, ADAR1 exerts a pro- or anti-viral role in vertebrates and Drosophila. RESULTS: We traced 4 ADAR homologs in 14 lophotrochozoan genomes and we classified them into ADAD, ADAR1 or ADAR2, based on phylogenetic and structural analyses of the enzymatic domain. Using RNA-seq and quantitative real time PCR we demonstrated the upregulation of one ADAR1 homolog in the bivalve Crassostrea gigas and in the gastropod Haliotis diversicolor supertexta during Ostreid herpesvirus-1 or Haliotid herpesvirus-1 infection. Accordingly, we demonstrated an extensive ADAR-mediated editing of viral RNAs. Single nucleotide variation (SNV) profiles obtained by pairing RNA- and DNA-seq data from the viral infected individuals resulted to be mostly compatible with ADAR-mediated A-to-I editing (up to 97%). SNVs occurred at low frequency in genomic hotspots, denoted by the overlapping of viral genes encoded on opposite DNA strands. The SNV sites and their upstream neighbor nucleotide indicated the targeting of selected adenosines. The analysis of viral sequences suggested that, under the pressure of the ADAR editing, the two Malacoherpesviridae genomes have evolved to reduce the number of deamination targets. CONCLUSIONS: We report, for the first time, evidence of an extensive editing of Malacoherpesviridae RNAs attributable to host ADAR1 enzymes. The analysis of base neighbor preferences, structural features and expression profiles of molluscan ADAR1 supports the conservation of the enzyme function among metazoans and further suggested that ADAR1 exerts an antiviral role in mollusks.


Assuntos
Antivirais/metabolismo , Vírus de DNA/genética , Moluscos/virologia , Edição de RNA/genética , RNA Viral/genética , Proteínas de Ligação a RNA/metabolismo , Animais , Teorema de Bayes , Vírus de DNA/fisiologia , Regulação da Expressão Gênica , Genoma Viral , Modelos Moleculares , Moluscos/genética , Filogenia , Polimorfismo de Nucleotídeo Único/genética , Domínios Proteicos , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética , Transcriptoma/genética
11.
Nat Biotechnol ; 37(9): 1059-1069, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31308540

RESUMO

Current tools for targeted RNA editing rely on the delivery of exogenous proteins or chemically modified guide RNAs, which may lead to aberrant effector activity, delivery barrier or immunogenicity. Here, we present an approach, called leveraging endogenous ADAR for programmable editing of RNA (LEAPER), that employs short engineered ADAR-recruiting RNAs (arRNAs) to recruit native ADAR1 or ADAR2 enzymes to change a specific adenosine to inosine. We show that arRNA, delivered by a plasmid or viral vector or as a synthetic oligonucleotide, achieves editing efficiencies of up to 80%. LEAPER is highly specific, with rare global off-targets and limited editing of non-target adenosines in the target region. It is active in a broad spectrum of cell types, including multiple human primary cell types, and can restore α-L-iduronidase catalytic activity in Hurler syndrome patient-derived primary fibroblasts without evoking innate immune responses. As a single-molecule system, LEAPER enables precise, efficient RNA editing with broad applicability for therapy and basic research.


Assuntos
Adenosina Desaminase/classificação , Adenosina Desaminase/metabolismo , Edição de RNA , Proteínas de Ligação a RNA/metabolismo , RNA/genética , Adenosina Desaminase/genética , Animais , Linhagem Celular , Engenharia Genética , Humanos , Proteínas de Ligação a RNA/genética
12.
Cells ; 8(7)2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284505

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs that are critical in post-transcriptional regulation. Macaca mulatta is an important nonhuman primate that is often used in basic and translational researches. However, the annotation of miRNAs in Macaca mulatta is far from complete, and there are no reports of miRNA editing events in Macaca mulatta, although editing may affect the biogenesis or functions of the miRNAs. To improve miRNA annotation and to reveal editing events of miRNAs in Macaca mulatta, we generated 12 small RNA profiles from eight tissues and performed comprehensive analysis of these profiles. We identified 479 conserved pre-miRNAs that have not been reported in Macaca mulatta and 17 species specific miRNAs. Furthermore, we identified 3386 editing sites with significant editing levels from 471 pre-miRNAs after analyzing the 12 self-generated and 58 additional published sRNA-seq profiles from 17 different types of organs or tissues. In addition to 16 conserved A-to-I editing sites, we identified five conserved C-to-U editing sites in miRNAs of Macaca mulatta and Homo sapiens. We also identified 11 SNPs in the miRNAs of Macaca mulatta. The analysis of the potential targets of 69 miRNAs with editing or mutation events in their seed regions suggest that these editing or mutation events severely changed their targets and their potential functions. These results significantly increase our understanding of miRNAs and their mutation/editing events in Macaca mulatta.


Assuntos
Macaca mulatta/genética , MicroRNAs/genética , Edição de RNA , Animais , Regulação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Anotação de Sequência Molecular , Mutação , Polimorfismo de Nucleotídeo Único , Especificidade da Espécie
13.
Plant Cell Physiol ; 60(9): 1927-1938, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31329953

RESUMO

Plants encode over 1800 RNA-binding proteins (RBPs) that modulate a myriad of steps in gene regulation from chromatin organization to translation, yet only a small number of these proteins and their target transcripts have been functionally characterized. Two classes of eukaryotic RBPs, pentatricopeptide repeat (PPR) and pumilio/fem-3 binding factors (PUF), recognize and bind to specific sequential RNA sequences through protein-RNA interactions. These modular proteins possess helical structural units containing key residues with high affinity for specific nucleotides, whose sequential order determines binding to a specific target RNA sequence. PPR proteins are nucleus-encoded, but largely regulate post-transcriptional gene regulation within plastids and mitochondria, including splicing, translation and RNA editing. Plant PUFs are involved in gene regulatory processes within the cell nucleus and cytoplasm. The modular structures of PPRs and PUFs that determine sequence specificity has facilitated identification of their RNA targets and biological functions. The protein-based RNA-targeting of PPRs and PUFs contrasts to the prokaryotic cluster regularly interspaced short palindromic repeats (CRISPR)-associated proteins (Cas) that target RNAs in prokaryotes. Together the PPR, PUF and CRISPR-Cas systems provide varied opportunities for RNA-targeted engineering applications.


Assuntos
Plantas/genética , Edição de RNA , Proteínas de Ligação a RNA/genética , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Plastídeos/metabolismo , RNA/genética , RNA/metabolismo , Proteínas de Ligação a RNA/metabolismo
14.
Anim Genet ; 50(5): 460-474, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31355950

RESUMO

RNA editing is a post-transcription maturation process that diversifies genomically encoded information and can lead to transcriptome diversity. Thanks to next-generation sequencing technologies, a large number of editing sites have been identified in different species. Although this mechanism is well described in mammals, only a few studies have been performed in chicken. Here, candidate or potential RNA editing sites were identified in eight different tissues of chicken (brain, spleen, colon, lung, kidney, heart, testes and liver). We identified 68 A-to-G editing sites in 46 genes. Only two of these were previously reported in chicken. We found no C-to-T sites, attesting to the lack of this type of editing mechanism in chicken. Similar to mammals, the editing sites were enriched in non-coding regions, rarely resulted in a change in amino acids, showed a critical role in the nervous system and had a low guanosine level upstream of the editing site and some enrichment downstream from the site. Moreover, in contrast to mammals, editing sites were weakly enriched in interspersed repeats and the number and editing ratio of non-synonymous sites were higher than for those of synonymous sites. Interestingly, we found several tissue-specific edited genes, including GABRA3, SORL1 and HTR1D in brain and RYR2 and FHOD3 in heart, that were associated with functional processes relevant to the corresponding tissue. This finding highlights the importance of RNA editing in several chicken tissues, especially the brain, and establishes a foundation for further exploration of this process.


Assuntos
Galinhas/genética , Especificidade de Órgãos , Edição de RNA , Animais , Transcriptoma
15.
RNA ; 25(9): 1150-1163, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31171708

RESUMO

Multiprotein editosomes catalyze gRNA-specified insertion and deletion of uridines to create functional mitochondrial mRNAs in Trypanosoma brucei Three functionally distinct editosomes are distinguished by their single KREN1, KREN2, or KREN3 RNase III endonuclease and, respectively, KREPB8, KREPB7, and KREPB6 partner proteins. These endonucleases perform the first catalytic step of editing, cleaving mRNA in diverse mRNA/gRNA heteroduplex substrates. We identified divergent and likely noncatalytic RNase III domains in KREPB4, KREPB5, KREPB6, KREPB7, KREPB8, KREPB9, and KREPB10 editosome proteins. Because known RNase III endonuclease functional domains are dimeric, the editing endonucleases may form heterodimers with one or more of these divergent RNase III proteins. We show here using conditional null cell lines that KREPB6, KREPB7, and KREPB8 are essential in both procyclic form (PF) and bloodstream (BF) cells. Loss of these proteins results in growth defects and loss of editing in vivo, as does mutation of their RNase III domain that is predicted to prevent dimerization. Loss of KREPB6, KREPB7, or KREPB8 also dramatically reduces cognate endonuclease abundance, as does the RNase III mutation, indicating that RNase III interactions with their partner proteins stabilize the endonucleases. The phenotypic consequences of repression are more severe in BF than in PF, indicating differences in endonuclease function between developmental stages that could impact regulation of editing. These results suggest that KREPB6, KREPB7, and KREPB8 form heterodimers with their respective endonucleases to perform mRNA cleavage. We also present a model wherein editosome proteins with divergent RNase III domains function in substrate selection via enzyme-pseudoenzyme interactions.


Assuntos
Proteínas de Protozoários/genética , Edição de RNA/genética , Ribonuclease III/genética , Trypanosoma brucei brucei/genética , Animais , Linhagem Celular , Endonucleases/genética , Mutação/genética , RNA Guia/genética , RNA Mensageiro/genética , RNA Mitocondrial/genética , RNA de Protozoário/genética , Uridina/genética
16.
Int J Mol Sci ; 20(13)2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31252669

RESUMO

Recent progress in the research for underlying mechanisms in neurodegenerative diseases, including Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) has led to the development of potentially effective treatment, and hence increased the need for useful biomarkers that may enable early diagnosis and therapeutic monitoring. The deposition of abnormal proteins is a pathological hallmark of neurodegenerative diseases, including ß-amyloid in AD, α-synuclein in PD, and the transactive response DNA/RNA binding protein of 43kDa (TDP-43) in ALS. Furthermore, progression of the disease process accompanies the spreading of abnormal proteins. Extracellular proteins and RNAs, including mRNA, micro RNA, and circular RNA, which are present as a composite of exosomes or other forms, play a role in cell-cell communication, and the role of extracellular molecules in the cell-to-cell spreading of pathological processes in neurodegenerative diseases is now in the spotlight. Therefore, extracellular proteins and RNAs are considered potential biomarkers of neurodegenerative diseases, in particular ALS, in which RNA dysregulation has been shown to be involved in the pathogenesis. Here, we review extracellular proteins and RNAs that have been scrutinized as potential biomarkers of neurodegenerative diseases, and discuss the possibility of extracellular RNAs as diagnostic and therapeutic monitoring biomarkers of sporadic ALS.


Assuntos
Esclerose Amiotrófica Lateral/sangue , Ácidos Nucleicos Livres/sangue , Esclerose Amiotrófica Lateral/genética , Animais , Biomarcadores/sangue , Ácidos Nucleicos Livres/genética , Humanos , Edição de RNA
17.
Int J Mol Sci ; 20(11)2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31163577

RESUMO

Energetically speaking, ribosome biogenesis is by far the most costly process of the cell and, therefore, must be highly regulated in order to avoid unnecessary energy expenditure. Not only must ribosomal RNA (rRNA) synthesis, ribosomal protein (RP) transcription, translation, and nuclear import, as well as ribosome assembly, be tightly controlled, these events must be coordinated with other cellular events, such as cell division and differentiation. In addition, ribosome biogenesis must respond rapidly to environmental cues mediated by internal and cell surface receptors, or stress (oxidative stress, DNA damage, amino acid depletion, etc.). This review examines some of the well-studied pathways known to control ribosome biogenesis (PI3K-AKT-mTOR, RB-p53, MYC) and how they may interact with some of the less well studied pathways (eIF2α kinase and RNA editing/splicing) in higher eukaryotes to regulate ribosome biogenesis, assembly, and protein translation in a dynamic manner.


Assuntos
Biossíntese de Proteínas , Ribossomos/metabolismo , Transdução de Sinais , Animais , Biomarcadores , Ciclo Celular/genética , Suscetibilidade a Doenças , Fator de Iniciação 2 em Eucariotos/metabolismo , Espaço Extracelular/metabolismo , Genes myc , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Edição de RNA , Processamento de RNA , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , Estresse Fisiológico , Serina-Treonina Quinases TOR/metabolismo , Transcrição Genética
18.
J Plant Physiol ; 240: 152992, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31234031

RESUMO

The recently identified PPR-E+/NVWA/DYW2 RNA editing complex provides insights into the mechanism of RNA editing in higher plant organelles. However, whether the complex works together with the previously identified editing factors RIPs/MORFs is unclear. In this paper, we identified a maize Smk6 gene, which encodes a mitochondrion-targeted PPR-E+protein with E1 and E2 domains at the C terminus. Loss of Smk6 function affects the C-to-U editing at nad1-740, nad4L-110, nad7-739, and mttB-138,139 sites, impairs mitochondrial activity and blocks embryogenesis and endosperm development. Genetic and molecular analysis indicated that SMK6 is the maize ortholog of the Arabidopsis SLO2, which is a component of the PPR-E+/NVWA/DYW2 editing complex. However, yeast two-hybrid analyses did not detect any interaction between SMK6 and any of the mitochondrion-targeted RIPs/MORFs, suggesting that RIPs/MORFs may not be a component of PPR-E+/NVWA/DYW2 RNA editing complex. Further analyses are required to provide evidence that RIP/MORFs and SMK6 do not physically interact in vivo.


Assuntos
Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Edição de RNA , Zea mays/genética , Sequência de Aminoácidos , Sequência de Bases , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Proteínas de Plantas/metabolismo , Alinhamento de Sequência , Zea mays/metabolismo
19.
DNA Res ; 26(3): 261-272, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31231762

RESUMO

Adenosine-to-inosine (A-to-I) RNA editing meditated by adenosine deaminases acting on RNA (ADARs) enzymes is a widespread post-transcriptional event in mammals. However, A-to-I editing in skeletal muscle remains poorly understood. By integrating strand-specific RNA-seq, whole genome bisulphite sequencing, and genome sequencing data, we comprehensively profiled the A-to-I editome in developing skeletal muscles across 27 prenatal and postnatal stages in pig, an important farm animal and biomedical model. We detected 198,892 A-to-I editing sites and found that they occurred more frequently at prenatal stages and showed low conservation among pig, human, and mouse. Both the editing level and frequency decreased during development and were positively correlated with ADAR enzymes expression. The hyper-edited genes were functionally related to the cell cycle and cell division. A co-editing module associated with myogenesis was identified. The developmentally differential editing sites were functionally enriched in genes associated with muscle development, their editing levels were highly correlated with expression of their host mRNAs, and they potentially influenced the gain/loss of miRNA binding sites. Finally, we developed a database to visualize the Sus scrofa RNA editome. Our study presents the first profile of the dynamic A-to-I editome in developing animal skeletal muscle and provides evidences that RNA editing is a vital regulator of myogenesis.


Assuntos
Adenosina Desaminase/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Edição de RNA , RNA Mensageiro/metabolismo , Sus scrofa/crescimento & desenvolvimento , Adenosina Desaminase/genética , Animais , Bases de Dados Genéticas , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Músculo Esquelético/enzimologia , Músculo Esquelético/metabolismo , Análise de Sequência de RNA , Sus scrofa/genética , Sus scrofa/metabolismo , Sequenciamento Completo do Genoma
20.
RNA ; 25(9): 1177-1191, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31221726

RESUMO

Uridine insertion deletion editing in kinetoplastid protozoa requires a complex machinery, a primary component of which is the RNA editing substrate binding complex (RESC). RESC contains two modules termed GRBC (guide RNA binding complex) and REMC (RNA editing mediator complex), although how interactions between these modules and their mRNA and gRNA binding partners are controlled is not well understood. Here, we demonstrate that the ARM/HEAT repeat containing RESC protein, MRB10130, controls REMC association with mRNA- and gRNA-loaded GRBC. High-throughput sequencing analyses show that MRB10130 functions in both initiation and 3' to 5' progression of editing through gRNA-defined domains. Editing intermediates that accumulate upon MRB10130 depletion significantly intersect those in cells depleted of another RESC organizer, MRB7260, but are distinct from those in cells depleted of specific REMC proteins. We present a model in which MRB10130 coordinates numerous protein-protein and protein-RNA interactions during editing progression.


Assuntos
Edição de RNA/genética , Animais , Linhagem Celular , Domínios e Motivos de Interação entre Proteínas/genética , Proteínas de Protozoários/genética , Interferência de RNA/fisiologia , RNA Guia/genética , RNA Mensageiro/genética , RNA de Protozoário/genética , Trypanosoma brucei brucei/genética , Uridina/genética
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