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1.
Cell Death Dis ; 15(6): 404, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858355

RESUMO

Senescent cells exhibit a diverse spectrum of changes in their morphology, proliferative capacity, senescence-associated secretory phenotype (SASP) production, and mitochondrial homeostasis. These cells often manifest with elongated mitochondria, a hallmark of cellular senescence. However, the precise regulatory mechanisms orchestrating this phenomenon remain predominantly unexplored. In this study, we provide compelling evidence for decreases in TIA-1, a pivotal regulator of mitochondrial dynamics, in models of both replicative senescence and ionizing radiation (IR)-induced senescence. The downregulation of TIA-1 was determined to trigger mitochondrial elongation and enhance the expression of senescence-associated ß-galactosidase, a marker of cellular senescence, in human foreskin fibroblast HS27 cells and human keratinocyte HaCaT cells. Conversely, the overexpression of TIA-1 mitigated IR-induced cellular senescence. Notably, we identified the miR-30-5p family as a novel factor regulating TIA-1 expression. Augmented expression of the miR-30-5p family was responsible for driving mitochondrial elongation and promoting cellular senescence in response to IR. Taken together, our findings underscore the significance of the miR-30-5p/TIA-1 axis in governing mitochondrial dynamics and cellular senescence.


Assuntos
Senescência Celular , MicroRNAs , Mitocôndrias , Dinâmica Mitocondrial , Antígeno-1 Intracelular de Células T , Humanos , MicroRNAs/metabolismo , MicroRNAs/genética , Senescência Celular/efeitos da radiação , Senescência Celular/genética , Dinâmica Mitocondrial/genética , Antígeno-1 Intracelular de Células T/metabolismo , Antígeno-1 Intracelular de Células T/genética , Mitocôndrias/metabolismo , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Linhagem Celular , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Queratinócitos/citologia , Transdução de Sinais , Radiação Ionizante
4.
Biochem Biophys Res Commun ; 530(1): 266-272, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32828297

RESUMO

Glucagon is a peptide hormone generated by pancreatic α cells. It is the counterpart of insulin and plays an essential role in the regulation of blood glucose level. Therefore, a tight regulation of glucagon levels is pivotal to maintain homeostasis of blood glucose. However, little is known about the mechanisms regulating glucagon biosynthesis. In this study, we demonstrate that the RNA-binding protein HuD regulates glucagon expression in pancreatic α cells. HuD was found in α cells from mouse pancreatic islet and mouse glucagonoma αTC1 cell line. Ribonucleoprotein immunoprecipitation analysis, followed by RT-qPCR showed the association of HuD with glucagon mRNA. Knockdown of HuD resulted in a reduction in both proglucagon expression and cellular glucagon level by decreasing its de novo synthesis. Reporter analysis using the EGFP reporter containing 3' untranslated region (3'UTR) of glucagon mRNA showed that HuD regulates proglucagon expression via its 3'UTR. In addition, the relative level of glucagon in the islets and plasma was lower in HuD knockout (KO) mice compared to age-matched control mice. Taken together, these results suggest that HuD is a novel factor regulating the biosynthesis of proglucagon in pancreatic α cells.


Assuntos
Proteína Semelhante a ELAV 4/metabolismo , Células Secretoras de Glucagon/metabolismo , Proglucagon/metabolismo , Animais , Vias Biossintéticas , Linhagem Celular , Linhagem Celular Tumoral , Regulação para Baixo , Proteína Semelhante a ELAV 4/genética , Técnicas de Silenciamento de Genes , Células Secretoras de Glucagon/citologia , Camundongos , Proglucagon/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
5.
Cell Death Differ ; 27(5): 1633-1643, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31659282

RESUMO

Imbalanced mitochondrial dynamics in pancreatic ß-cells contributes to ß-cell dysfunction in diabetes; however, the molecular mechanisms underlying mitochondrial dynamics in the pathology of diabetes are not fully elucidated. We previously reported the reduction of RNA binding protein HuD in pancreatic ß-cells of diabetes. Herein, we demonstrate that HuD plays a novel role in the regulation of mitochondrial dynamics by promoting mitochondrial fusion. We show enhanced mitochondrial fragmentation in the pancreas of db/db mice and HuD KO mice. Downregulation of HuD increases the number of cells with fragmented mitochondria and reduces the mitochondrial activity determined by mitochondrial membrane potential and ATP production in mouse insulinoma ßTC6 cells. HuD binds to 3'-untraslated region of mitofusin 2 (Mfn2) mRNA and positively regulates its expression. Ectopic expression of Mfn2 in ßTC6 cells stably expressing short hairpin RNA against HuD (shHuD) restores HuD-mediated mitochondrial dysfunction. Taken together, our results suggest that HuD regulates mitochondrial dynamics by regulating Mfn2 level and its reduced expression leads to mitochondrial dysfunction in pancreatic ß-cells.


Assuntos
Proteína Semelhante a ELAV 4/metabolismo , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Dinâmica Mitocondrial , Animais , Linhagem Celular , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Regulação da Expressão Gênica , Camundongos Knockout , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Dinâmica Mitocondrial/genética , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
6.
J Pathol ; 249(3): 395-408, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31301177

RESUMO

Polypyrimidine tract-binding protein 1 (PTBP1) is one of the most investigated multifunctional RNA-binding proteins (RBP), controlling almost all steps of mRNA metabolism and processing. It has been reported that PTBP1 is overexpressed in many different types of cancer and this high expression is associated with increased proliferation and poor prognoses. However, there are no reports on a putative role for PTBP1 in the molecular abnormalities and pathogenesis of hepatocellular carcinoma (HCC). Here, we identified PTBP1 as a positive regulator of human HCC growth. The expression of PTBP1 was increased in human HCC cells and tissues compared to the corresponding controls, and this high expression was positively correlated with increased tumor size and a reduced survival rate. Mechanistically, PTBP1 enhanced cyclin D3 (CCND3) translation by interacting with the 5'-untranslated region (5'-UTR) of CCND3 mRNA, consequently facilitating cell cycle progression and tumor growth. Furthermore, we found that miR-194 inhibits PTBP1 expression by binding to the 3'-UTR of PTBP1 mRNA, resulting in reduced CCND3 levels and HCC cell growth; moreover, the levels of PTBP1 were negatively correlated with miR-194 levels in HCC. Taken together, these findings identify PTBP1 as a pivotal enhancer of HCC growth; the miR-194/PTBP1/CCND3 axis seemingly has a crucial role in the development and progression of HCC and targeting the axis could be a novel therapeutic strategy against human HCC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Carcinoma Hepatocelular/metabolismo , Proliferação de Células , Ciclina D3/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Regiões 3' não Traduzidas , Regiões 5' não Traduzidas , Animais , Sítios de Ligação , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Ciclina D3/genética , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Transdução de Sinais , Carga Tumoral , Células Tumorais Cultivadas
7.
Mol Cell Biol ; 39(6)2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30602494

RESUMO

Autophagy is a process of lysosomal self-degradation of cellular components by forming autophagosomes. Autophagosome formation is an essential process in autophagy and is fine-tuned by various autophagy-related gene (ATG) products, including ATG5, ATG12, and ATG16. Although several reports have shown that numerous factors affect multiple levels of gene regulation to orchestrate cellular autophagy, the detailed mechanism of autophagosome formation still needs further investigation. In this study, we demonstrate that the RNA binding protein HuR (human antigen R) performs an essential function in autophagosome formation. We observe that HuR silencing leads to inhibition of autophagosome formation and autophagic flux in liver cells. Ribonucleoprotein immunoprecipitation (RIP) assay allows the identification of ATG5, ATG12, and ATG16 mRNAs as the direct targets of HuR. We further show that HuR mediates the translation of ATG5, ATG12, and ATG16 mRNAs by binding to their 3' untranslated regions (UTRs). In addition, we show that HuR expression positively correlates with the levels of ATG5 and ATG12 in hepatocellular carcinoma (HCC) cells. Collectively, our results suggest that HuR functions as a pivotal regulator of autophagosome formation by enhancing the translation of ATG5, ATG12, and ATG16 mRNAs and that augmented expression of HuR and ATGs may participate in the malfunction of autophagy in HCC cells.


Assuntos
Autofagossomos/metabolismo , Proteínas Relacionadas à Autofagia/biossíntese , Carcinoma Hepatocelular/metabolismo , Proteína Semelhante a ELAV 1/metabolismo , Neoplasias Hepáticas/metabolismo , Autofagia/genética , Autofagia/fisiologia , Proteína 12 Relacionada à Autofagia/genética , Proteína 12 Relacionada à Autofagia/metabolismo , Proteína 5 Relacionada à Autofagia/metabolismo , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proteína Semelhante a ELAV 1/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Proteínas Associadas aos Microtúbulos/metabolismo , Fagossomos/metabolismo , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
8.
Biochem Biophys Res Commun ; 497(4): 1117-1122, 2018 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-29496454

RESUMO

Precise and early diagnosis is critical to improve the survival rate of hepatocellular carcinoma (HCC) patients. Although several genetic and protein markers have been developed and are currently used for diagnosis, prognosis, risk stratification, and therapeutic monitoring, application of these markers still needs to be improved for better specificity and efficacy. In this study, we investigated the relative expression of mitochondrial dynamics-regulating factors including T-cell intercellular antigen protein-1 (TIA-1), mitochondrial fission factor (MFF), microRNA (miR)-200a-3p, and miR-27a/b in the liver tissues from HCC patients. The expressions of TIA-1 and MFF were augmented in the cancerous liver tissues compared to the corresponding non-tumor tissues at mRNA and protein level, while the levels of miR-200a-3p and miR-27a/b were relatively lower in the cancerous liver tissues. In addition, high levels of TIA-1 and MFF mRNA were related to the poor survival rate of HCC patients. Our results indicated that the expressions of TIA-1, MFF, miR-200a-3p, and miR-27a/b in the cancerous liver tissues differed to these in non-cancerous tissues of HCC patients, demonstrating that these gene expressions could be potential markers for the diagnosis and prognosis of HCC.


Assuntos
Biomarcadores/análise , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Proteínas de Membrana/análise , MicroRNAs/análise , Proteínas Mitocondriais/análise , Taxa de Sobrevida , Antígeno-1 Intracelular de Células T/análise
9.
Exp Mol Med ; 49(5): e327, 2017 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-28496200

RESUMO

Acquisition of resistance to anti-cancer drugs is a significant obstacle to effective cancer treatment. Although several efforts have been made to overcome drug resistance in cancer cells, the detailed mechanisms have not been fully elucidated. Here, we investigated whether microRNAs (miRNAs) function as pivotal regulators in the acquisition of anti-cancer drug resistance to 5-fluorouracil (5-FU). A survey using a lentivirus library containing 572 precursor miRNAs revealed that five miRNAs promoted cell survival after 5-FU treatment in human hepatocellular carcinoma Hep3B cells. Among the five different clones, the clone expressing miR-200a-3p (Hep3B-miR-200a-3p) was further characterized as a 5-FU-resistant cell line. The cell viability and growth rate of Hep3B-miR-200a-3p cells were higher than those of control cells after 5-FU treatment. Ectopic expression of a miR-200a-3p mimic increased, while inhibition of miR-200a-3p downregulated, cell viability in response to 5-FU, doxorubicin, and CDDP (cisplatin). We also showed that dual-specificity phosphatase 6 (DUSP6) is a novel target of miR-200a-3p and regulates resistance to 5-FU. Ectopic expression of DUSP6 mitigated the pro-survival effects of miR-200a-3p. Taken together, these results lead us to propose that miR-200a-3p enhances anti-cancer drug resistance by decreasing DUSP6 expression.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Fosfatase 6 de Especificidade Dupla/metabolismo , Fluoruracila/farmacologia , MicroRNAs/genética , Linhagem Celular Tumoral , Cisplatino/farmacologia , Doxorrubicina/farmacologia , Fosfatase 6 de Especificidade Dupla/genética , Humanos , MicroRNAs/metabolismo
10.
Sci Rep ; 7: 44847, 2017 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-28337997

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression by suppressing translation or facilitating mRNA decay. Differential expression of miRNAs is involved in the pathogenesis of several diseases including cancer. Here, we investigated the role of-miR-24-3p as a downregulated miRNA in metastatic cancer. miR-24-3p was decreased in metastatic cancer and lower expression of miR-24-3p was related to poor survival of cancer patients. Consistently, ectopic expression of miR-24-3p suppressed the cell migration, invasion, and proliferation of MCF7, Hep3B, B16F10, SK-Hep1, and PC-3 cells by directly targeting p130Cas. Stable expression of p130Cas restored miR-24-3p-mediated inhibition of cell migration and invasion. These results suggest that miR-24-3p functions as a tumor suppressor and the miR-24-3p/p130Cas axis is a novel factor of cancer progression by regulating cell migration and invasion.


Assuntos
Proteína Substrato Associada a Crk/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Interferência de RNA , Regiões 3' não Traduzidas , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Humanos , Camundongos , Metástase Neoplásica , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/mortalidade , Transcriptoma , Ensaios Antitumorais Modelo de Xenoenxerto
11.
BMB Rep ; 50(4): 214-219, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28148392

RESUMO

Mitochondria play pivotal roles in the ATP production, apoptosis and generation of reactive oxygen species. Although dynamic regulation of mitochondria morphology is a critical step to maintain cellular homeostasis, the regulatory mechanisms are not yet fully elucidated. In this study, we identified miR-200a-3p as a novel regulator of mitochondrial dynamics by targeting mitochondrial fission factor (MFF). We demonstrated that the ectopic expression of miR-200a-3p enhanced mitochondrial elongation, mitochondrial ATP synthesis, mitochondrial membrane potential and oxygen consumption rate. These results indicate that miR-200a-3p positively regulates mitochondrial elongation by downregulating MFF expression. [BMB Reports 2017; 50(4): 214-219].


Assuntos
Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/fisiologia , Proteínas Mitocondriais/metabolismo , Regiões 3' não Traduzidas , Trifosfato de Adenosina/metabolismo , Antagomirs/metabolismo , Sequência de Bases , Linhagem Celular , Dinaminas , GTP Fosfo-Hidrolases/metabolismo , Humanos , Potencial da Membrana Mitocondrial , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Microscopia de Fluorescência , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas Mitocondriais/antagonistas & inibidores , Proteínas Mitocondriais/genética , Consumo de Oxigênio , Alinhamento de Sequência
12.
Cell Death Differ ; 24(1): 49-58, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27612012

RESUMO

Mitochondrial morphology is dynamically regulated by the formation of small fragmented units or interconnected mitochondrial networks, and this dynamic morphological change is a pivotal process in normal mitochondrial function. In the present study, we identified a novel regulator responsible for the regulation of mitochondrial dynamics. An assay using CHANG liver cells stably expressing mitochondrial-targeted yellow fluorescent protein (mtYFP) and a group of siRNAs revealed that T-cell intracellular antigen protein-1 (TIA-1) affects mitochondrial morphology by enhancing mitochondrial fission. The function of TIA-1 in mitochondrial dynamics was investigated through various biological approaches and expression analysis in human specimen. Downregulation of TIA-1-enhanced mitochondrial elongation, whereas ectopic expression of TIA-1 resulted in mitochondria fragmentation. In addition, TIA-1 increased mitochondrial activity, including the rate of ATP synthesis and oxygen consumption. Further, we identified mitochondrial fission factor (MFF) as a direct target of TIA-1, and showed that TIA-1 promotes mitochondrial fragmentation by enhancing MFF translation. TIA-1 null cells had a decreased level of MFF and less mitochondrial Drp1, a critical factor for mitochondrial fragmentation, thereby enhancing mitochondrial elongation. Taken together, our results indicate that TIA-1 is a novel factor that facilitates mitochondrial dynamics by enhancing MFF expression and contributes to mitochondrial dysfunction.


Assuntos
Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Antígeno-1 Intracelular de Células T/metabolismo , Regiões 3' não Traduzidas , Trifosfato de Adenosina/biossíntese , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Linhagem Celular , Dinaminas , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Humanos , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Camundongos , MicroRNAs/metabolismo , Microscopia de Fluorescência , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Mitocondriais/antagonistas & inibidores , Proteínas Mitocondriais/genética , Consumo de Oxigênio , Plasmídeos/genética , Plasmídeos/metabolismo , Interferência de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Antígeno-1 Intracelular de Células T/antagonistas & inibidores , Antígeno-1 Intracelular de Células T/genética
13.
Biochim Biophys Acta ; 1859(4): 675-85, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26945853

RESUMO

Although triglyceride (TG) accumulation in the pancreas leads to ß-cell dysfunction and raises the chance to develop metabolic disorders such as type 2 diabetes (T2DM), the molecular mechanisms whereby intracellular TG levels are regulated in pancreatic ß cells have not been fully elucidated. Here, we present evidence that the RNA-binding protein HuD regulates TG production in pancreatic ß cells. Mouse insulinoma ßTC6 cells stably expressing a small hairpin RNA targeting HuD (shHuD) (ßTC6-shHuD) contained higher TG levels compared to control cells. Moreover, downregulation of HuD resulted in a decrease in insulin-induced gene 1 (INSIG1) levels but not in the levels of sterol regulatory element-binding protein 1c (SREBP1c), a key transcription factor for lipid production. We identified Insig1 mRNA as a direct target of HuD by using ribonucleoprotein immunoprecipitation (RIP) and biotin pulldown analyses. By associating with the 3'-untranslated region (3'UTR) of Insig1 mRNA, HuD promoted INSIG1 translation; accordingly, HuD downregulation reduced while ectopic HuD expression increased INSIG1 levels. We further observed that HuD downregulation facilitated the nuclear localization of SREBP1c, thereby increasing the transcriptional activity of SREBP1c and the expression of target genes involved in lipogenesis; likewise, we observed lower INSIG1 levels in the pancreatic islets of HuD-null mice. Taken together, our results indicate that HuD functions as a novel repressor of lipid synthesis in pancreatic ß cells.


Assuntos
Diabetes Mellitus Tipo 2/genética , Proteína Semelhante a ELAV 4/metabolismo , Células Secretoras de Insulina/metabolismo , Proteínas de Ligação a RNA/metabolismo , Triglicerídeos/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Proteína Semelhante a ELAV 4/genética , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/patologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Proteínas de Ligação a RNA/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
14.
Exp Mol Med ; 46: e123, 2014 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-25431021

RESUMO

Mitochondrial morphology is dynamically regulated by forming small, fragmented units or interconnected networks, and this is a pivotal process that is used to maintain mitochondrial homeostasis. Although dysregulation of mitochondrial dynamics is related to the pathogenesis of several human diseases, its molecular mechanism is not fully elucidated. In this study, we demonstrate the potential role of miR-27 in the regulation of mitochondrial dynamics. Mitochondrial fission factor (MFF) mRNA is a direct target of miR-27, whose ectopic expression decreases MFF expression through binding to its 3'-untranslated region. Expression of miR-27 results in the elongation of mitochondria as well as an increased mitochondrial membrane potential and mitochondrial ATP level. Our results suggest that miR-27 is a novel regulator affecting morphological mitochondrial changes by targeting MFF.


Assuntos
Proteínas de Membrana/genética , MicroRNAs/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Proteínas Mitocondriais/genética , Biossíntese de Proteínas , Regiões 3' não Traduzidas , Linhagem Celular , Regulação da Expressão Gênica , Humanos , Potencial da Membrana Mitocondrial , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
15.
Biochem Biophys Res Commun ; 446(1): 218-23, 2014 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-24602614

RESUMO

Piwi-interacting RNAs (piRNAs) are 26-31 nt small noncoding RNAs that are processed from their longer precursor transcripts by Piwi proteins. Localization of Piwi and piRNA has been reported mostly in nucleus and cytoplasm of higher eukaryotes germ-line cells, where it is believed that known piRNA sequences are located in repeat regions of nuclear genome in germ-line cells. However, localization of PIWI and piRNA in mammalian somatic cell mitochondria yet remains largely unknown. We identified 29 piRNA sequence alignments from various regions of the human mitochondrial genome. Twelve out 29 piRNA sequences matched stem-loop fragment sequences of seven distinct tRNAs. We observed their actual expression in mitochondria subcellular fractions by inspecting mitochondrial-specific small RNA-Seq datasets. Of interest, the majority of the 29 piRNAs overlapped with multiple longer transcripts (expressed sequence tags) that are unique to the human mitochondrial genome. The presence of mature piRNAs in mitochondria was detected by qRT-PCR of mitochondrial subcellular RNAs. Further validation showed detection of Piwi by colocalization using anti-Piwil1 and mitochondria organelle-specific protein antibodies.


Assuntos
Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , RNA/genética , RNA/metabolismo , Linhagem Celular Tumoral , DNA Mitocondrial/genética , Etiquetas de Sequências Expressas , Genoma Mitocondrial , Células HEK293 , Células HeLa , Humanos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , RNA Mitocondrial , RNA Neoplásico/genética , RNA Neoplásico/metabolismo
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