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1.
PLoS One ; 16(5): e0250669, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33951080

RESUMO

Mature mRNA molecules are expected to be comprised of a 5'UTR, a 3'UTR and a coding region (CDS). Unexpectedly, however, there have been multiple recent reports of widespread differential expression of mRNA 3'UTRs and their cognate coding regions (CDS), reflecting the expression of isolated 3'UTRs (i3'UTRs); these i3'UTRs can be highly expressed, often in reciprocal patterns to their cognate CDS. As with other long non-coding (lncRNAs), isolated 3'UTRs are likely to play an important role in gene regulation, but little is known about the contexts in which they are deployed. To illuminate the functions of i3'UTRs, here we carry out in vitro, in vivo and in silico analyses of differential 3'UTR/CDS mRNA ratio usage across tissues, development and cell state changes both for a select list of developmentally important genes as well as by unbiased transcriptome-wide analyses. Across two developmental paradigms we find a distinct switch from high i3'UTR expression for stem cell related genes in proliferating cells to high CDS for these genes in newly differentiated cells. Unbiased transcriptome analysis across multiple gene sets shows that regardless of tissue, genes with high 3'UTR to CDS ratios belong predominantly to gene ontology categories related to cell-type specific functions. In contrast, the gene ontology categories of genes with low 3'UTR to CDS ratios are similar across tissues and relate to common cellular functions. We further show that, at least for some genes, traditional transcriptional start site genomic elements correspond to identified RNAseq 3'UTR peak regions, suggesting that some i3'UTRs may be generated by de novo transcription. Our results provide critical information from which detailed hypotheses for individual i3'UTRs can be tested, with a common theme that i3'UTRs appear poised to regulate cell-specific gene expression and state.


Assuntos
Regiões 3' não Traduzidas/genética , Perfilação da Expressão Gênica , Humanos , Poliadenilação
2.
Proc Natl Acad Sci U S A ; 117(40): 25074-25084, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32948690

RESUMO

We are only just beginning to catalog the vast diversity of cell types in the cerebral cortex. Such categorization is a first step toward understanding how diversification relates to function. All cortical projection neurons arise from a uniform pool of progenitor cells that lines the ventricles of the forebrain. It is still unclear how these progenitor cells generate the more than 50 unique types of mature cortical projection neurons defined by their distinct gene-expression profiles. Moreover, exactly how and when neurons diversify their function during development is unknown. Here we relate gene expression and chromatin accessibility of two subclasses of projection neurons with divergent morphological and functional features as they develop in the mouse brain between embryonic day 13 and postnatal day 5 in order to identify transcriptional networks that diversify neuron cell fate. We compare these gene-expression profiles with published profiles of single cells isolated from similar populations and establish that layer-defined cell classes encompass cell subtypes and developmental trajectories identified using single-cell sequencing. Given the depth of our sequencing, we identify groups of transcription factors with particularly dense subclass-specific regulation and subclass-enriched transcription factor binding motifs. We also describe transcription factor-adjacent long noncoding RNAs that define each subclass and validate the function of Myt1l in balancing the ratio of the two subclasses in vitro. Our multidimensional approach supports an evolving model of progressive restriction of cell fate competence through inherited transcriptional identities.


Assuntos
Proteínas do Tecido Nervoso/genética , Neurônios/metabolismo , Análise de Célula Única , Fatores de Transcrição/genética , Animais , Diferenciação Celular/genética , Córtex Cerebral/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Camundongos , RNA-Seq/métodos
3.
Elife ; 62017 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-28994391

RESUMO

Ethylene plays critical roles in plant development and biotic stress response, but the mechanism of ethylene in host antiviral response remains unclear. Here, we report that Rice dwarf virus (RDV) triggers ethylene production by stimulating the activity of S-adenosyl-L-methionine synthetase (SAMS), a key component of the ethylene synthesis pathway, resulting in elevated susceptibility to RDV. RDV-encoded Pns11 protein specifically interacted with OsSAMS1 to enhance its enzymatic activity, leading to higher ethylene levels in both RDV-infected and Pns11-overexpressing rice. Consistent with a counter-defense role for ethylene, Pns11-overexpressing rice, as well as those overexpressing OsSAMS1, were substantially more susceptible to RDV infection, and a similar effect was observed in rice plants treated with an ethylene precursor. Conversely, OsSAMS1-knockout mutants, as well as an osein2 mutant defective in ethylene signaling, resisted RDV infection more robustly. Our findings uncover a novel mechanism which RDV manipulates ethylene biosynthesis in the host plants to achieve efficient infection.


Assuntos
Etilenos/metabolismo , Interações Hospedeiro-Patógeno , Metionina Adenosiltransferase/metabolismo , Oryza/virologia , Vírus de Plantas/fisiologia , Proteínas Virais/metabolismo , Viroses , Técnicas de Inativação de Genes , Metionina Adenosiltransferase/genética
4.
PLoS Pathog ; 12(9): e1005847, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27606959

RESUMO

The phytohormone auxin plays critical roles in regulating myriads of plant growth and developmental processes. Microbe infection can disturb auxin signaling resulting in defects in these processes, but the underlying mechanisms are poorly understood. Auxin signaling begins with perception of auxin by a transient co-receptor complex consisting of an F-box transport inhibitor response 1/auxin signaling F-box (TIR1/AFB) protein and an auxin/indole-3-acetic acid (Aux/IAA) protein. Auxin binding to the co-receptor triggers ubiquitination and 26S proteasome degradation of the Aux/IAA proteins, leading to subsequent events, including expression of auxin-responsive genes. Here we report that Rice dwarf virus (RDV), a devastating pathogen of rice, causes disease symptoms including dwarfing, increased tiller number and short crown roots in infected rice as a result of reduced sensitivity to auxin signaling. The RDV capsid protein P2 binds OsIAA10, blocking the interaction between OsIAA10 and OsTIR1 and inhibiting 26S proteasome-mediated OsIAA10 degradation. Transgenic rice plants overexpressing wild-type or a dominant-negative (degradation-resistant) mutant of OsIAA10 phenocopy RDV symptoms are more susceptible to RDV infection; however, knockdown of OsIAA10 enhances the resistance of rice to RDV infection. Our findings reveal a previously unknown mechanism of viral protein reprogramming of a key step in auxin signaling initiation that enhances viral infection and pathogenesis.


Assuntos
Proteínas do Capsídeo/metabolismo , Ácidos Indolacéticos/metabolismo , Oryza/metabolismo , Doenças das Plantas/virologia , Proteínas de Plantas/metabolismo , Vírus de Plantas/metabolismo , Reoviridae/metabolismo , Transdução de Sinais , Proteínas do Capsídeo/genética , Oryza/genética , Oryza/virologia , Doenças das Plantas/genética , Proteínas de Plantas/genética , Vírus de Plantas/genética , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Reoviridae/genética
5.
Plant Cell ; 28(5): 1094-107, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27113774

RESUMO

Some DNA-dependent RNA polymerases (DdRPs) possess RNA-dependent RNA polymerase activity, as was first discovered in the replication of Potato spindle tuber viroid (PSTVd) RNA genome in tomato (Solanum lycopersicum). Recent studies revealed that this activity in bacteria and mammals is important for transcriptional and posttranscriptional regulatory mechanisms. Here, we used PSTVd as a model to uncover auxiliary factors essential for RNA-templated transcription by DdRP PSTVd replication in the nucleoplasm generates (-)-PSTVd intermediates and (+)-PSTVd copies. We found that the Nicotiana benthamiana canonical 9-zinc finger (ZF) Transcription Factor IIIA (TFIIIA-9ZF) as well as its variant TFIIIA-7ZF interacted with (+)-PSTVd, but only TFIIIA-7ZF interacted with (-)-PSTVd. Suppression of TFIIIA-7ZF reduced PSTVd replication, and overexpression of TFIIIA-7ZF enhanced PSTVd replication in planta. Consistent with the locale of PSTVd replication, TFIIIA-7ZF was found in the nucleoplasm and nucleolus, in contrast to the strictly nucleolar localization of TFIIIA-9ZF. Footprinting assays revealed that only TFIIIA-7ZF bound to a region of PSTVd critical for initiating transcription. Furthermore, TFIIIA-7ZF strongly enhanced the in vitro transcription of circular (+)-PSTVd by partially purified Pol II. Together, our results identify TFIIIA-7ZF as a dedicated cellular transcription factor that acts in DdRP-catalyzed RNA-templated transcription, highlighting both the extraordinary evolutionary adaptation of viroids and the potential of DdRPs for a broader role in cellular processes.


Assuntos
Nicotiana/metabolismo , Proteínas de Plantas/metabolismo , RNA Polimerase II/metabolismo , RNA não Traduzido/genética , Fatores de Transcrição/metabolismo , Proteínas de Plantas/genética , RNA Polimerase II/genética , Nicotiana/genética , Fator de Transcrição TFIIIA/genética , Fator de Transcrição TFIIIA/metabolismo , Fatores de Transcrição/genética
6.
Elife ; 42015 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-25688565

RESUMO

Viral pathogens are a major threat to rice production worldwide. Although RNA interference (RNAi) is known to mediate antiviral immunity in plant and animal models, the mechanism of antiviral RNAi in rice and other economically important crops is poorly understood. Here, we report that rice resistance to evolutionarily diverse viruses requires Argonaute18 (AGO18). Genetic studies reveal that the antiviral function of AGO18 depends on its activity to sequester microRNA168 (miR168) to alleviate repression of rice AGO1 essential for antiviral RNAi. Expression of miR168-resistant AGO1a in ago18 background rescues or increases rice antiviral activity. Notably, stable transgenic expression of AGO18 confers broad-spectrum virus resistance in rice. Our findings uncover a novel cooperative antiviral activity of two distinct AGO proteins and suggest a new strategy for the control of viral diseases in rice.


Assuntos
Proteínas Argonautas/fisiologia , Oryza/virologia , Proteínas Argonautas/genética , Humanos , Oryza/genética , Vírus de Plantas/patogenicidade
8.
Mol Cell Proteomics ; 7(9): 1737-47, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18515266

RESUMO

The liver is a complex and unique organ responsible for a breadth of functions crucial to sustaining life, especially for various metabolic processes in its mitochondria. Senescence-accelerated mouse prone/8 (SAMP8), a widely used aging model, exhibits an oxidative stress-induced aging phenotype and severe mitochondria-related liver pathology that are not seen in senescence-accelerated mouse resistant/1 (SAMR1). Here we used both two-dimensional electrophoresis- and ICAT-based mitochondrial proteomics analysis to view the liver mitochondrial protein alterations between SAMP8 and SAMR1. Compared with SAMR1, decreased expression and activity of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase were detected in SAMP8 at 6 months old (SAMP8-6m). As the key enzyme of ketogenesis, 3-hydroxy-3-methylglutaryl-CoA synthase is well known to be transcriptionally regulated by peroxisome proliferator-activated receptor alpha, which was also expressed at lower levels in SAMP8-6m livers. In addition, down-regulation of two peroxisome proliferator-activated receptor alpha target gene products (acyl-CoA oxidase and enoyl-CoA hydratase), elevation of triglyceride, and reduction of acetyl-CoA were observed, indicating abnormal fatty acid metabolism in SAMP8-6m livers. In addition eight proteins (NDUAA, NDUBA, NDUB7, NDUS1, NDUS3, NDUV1, ETFA, and UCRI) of mitochondrial complexes were down-regulated in SAMP8-6m, resulting in mitochondria-related liver dysfunction characterized by enhanced oxidative stress-induced molecular damage (lipid peroxide and oxidized protein) and depressed energy production (ATP). Glutamine synthetase and ornithine aminotransferase involved in glutamine synthesis were up-regulated in SAMP8 livers at both 1 and 6 months old that may be related to the accumulation of glutamate and glutamine. Our work provided useful clues to understanding the molecular mechanism underlying liver dysfunction in senescence-accelerated mouse.


Assuntos
Senilidade Prematura/enzimologia , Fígado/enzimologia , Mitocôndrias/enzimologia , Proteínas Mitocondriais/metabolismo , Proteômica/métodos , Trifosfato de Adenosina/metabolismo , Senilidade Prematura/genética , Senilidade Prematura/fisiopatologia , Animais , Modelos Animais de Doenças , Eletroforese em Gel Bidimensional , Fígado/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos , Proteínas Mitocondriais/análise
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