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1.
J Mol Cell Biol ; 16(3)2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-38509021

RESUMO

N 6,2'-O-dimethyladenosine (m6Am) is a prevalent modification frequently found at the 5' cap-adjacent adenosine of messenger RNAs (mRNAs) and small nuclear RNAs (snRNAs) and the internal adenosine of snRNAs. This dynamic and reversible modification is under the regulation of methyltransferases phosphorylated CTD interacting factor 1 and methyltransferase-like protein 4, along with the demethylase fat mass and obesity-associated protein. m6Am RNA modification plays a crucial role in the regulation of pre-mRNA splicing, mRNA stability, and translation, thereby influencing gene expression. In recent years, there has been growing interest in exploring the functions of m6Am and its relevance to human diseases. In this review, we provide a comprehensive overview of the current knowledge concerning m6Am, with a focus on m6Am-modifying enzymes, sequencing approaches for its detection, and its impacts on pre-mRNA splicing, mRNA stability, and translation regulation. Furthermore, we highlight the roles of m6Am in the context of obesity, viral infections, and cancers, unravelling its underlying regulatory mechanisms.


Assuntos
Adenosina , Humanos , Adenosina/metabolismo , Adenosina/análogos & derivados , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Splicing de RNA/genética , Obesidade/metabolismo , Obesidade/genética , Neoplasias/genética , Neoplasias/metabolismo , Estabilidade de RNA/genética , Metilação , Metiltransferases/metabolismo , Metiltransferases/genética , Processamento Pós-Transcricional do RNA , Animais , RNA Nuclear Pequeno/metabolismo , RNA Nuclear Pequeno/genética , Viroses/genética , Viroses/metabolismo , Regulação da Expressão Gênica
2.
FEBS J ; 290(10): 2590-2603, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35633520

RESUMO

Cilia are microtubule-based organelles that protrude from the cell surface and play crucial roles in cellular signaling pathways and extracellular fluid movement. Defects in the ciliary structures and functions are implicated in a set of hereditary disorders, including polycystic kidney disease, nephronophthisis, and Bardet-Biedl syndrome, which are collectively termed as ciliopathies. The application of mass spectrometry-based proteomic approaches to explore ciliary components provides important clues for understanding their physiological and pathological roles. In this review, we focus primarily on proteomic studies involving the identification of proteins in motile cilia and primary cilia, proteomes in ciliopathies, and interactomes of ciliopathy proteins. Collectively, the integration of these data sets will be beneficial for the comprehensive understanding of ciliary structures and exploring potential biomarkers and therapeutic targets for ciliopathies.


Assuntos
Ciliopatias , Doenças Renais Policísticas , Humanos , Proteômica , Cílios/metabolismo , Ciliopatias/genética , Doenças Renais Policísticas/metabolismo
3.
Biosens Bioelectron ; 129: 216-223, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30297172

RESUMO

Parkinson's disease caused by lack of dopamine in brain is a common neurodegenerative disorder. The traditional treatment is to replenish levodopa since it could pass through blood brain barrier and form dopamine. However, its accumulation can cause patients' movement disorders and uncontrollable emotion. Therefore, it is critical to control the levodopa dosage accuracy to improve the curative effect in clinical. In this study, a smartphone-based electrochemical detection system was developed for rapid monitoring of levodopa. The system involved a disposable sensor, a hand-held electrochemical detector, and a smartphone with designed application. Single-wall carbon nanotubes and gold nanoparticles modified screen-printed electrodes were used to convert and amplify the electrochemical current signals upon presence of levodopa molecules. The electrochemical detectors were used to generate electrochemical excitation signals and detect the resultant currents. Smartphone was connected to the detector, which was used to control the detector, calculate data, and plot graph in real-time. The smartphone-based differential pulse amperometry system was demonstrated to monitor levodopa at concentrations as low as 0.5 µM in human serum. Furthermore, it has also been verified to be able to distinguish levodopa from other representative substances in the body. Therefore, its performance was more sensitive and rapid than electrochemical workstation. With these advantages, the system can be used in the field of point-of-care testing (POCT) to detect levodopa and provide the possibility to solve clinical demand for levodopa detection.


Assuntos
Antiparkinsonianos/sangue , Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/instrumentação , Ouro/química , Levodopa/sangue , Nanopartículas Metálicas/química , Nanotubos de Carbono/química , Monitoramento de Medicamentos/instrumentação , Eletrodos , Desenho de Equipamento , Humanos , Limite de Detecção , Modelos Moleculares , Doença de Parkinson/tratamento farmacológico , Smartphone
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