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1.
Nucleic Acids Res ; 49(12): 6722-6738, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34125914

RESUMO

The m7G cap is ubiquitous on RNAPII-transcribed RNA and has fundamental roles in eukaryotic gene expression, however its in vivo role in mammals has remained unknown. Here, we identified the m7G cap methyltransferase, RNMT, as a key mediator of T cell activation, which specifically regulates ribosome production. During T cell activation, induction of mRNA expression and ribosome biogenesis drives metabolic reprogramming, rapid proliferation and differentiation generating effector populations. We report that RNMT is induced by T cell receptor (TCR) stimulation and co-ordinates the mRNA, snoRNA and rRNA production required for ribosome biogenesis. Using transcriptomic and proteomic analyses, we demonstrate that RNMT selectively regulates the expression of terminal polypyrimidine tract (TOP) mRNAs, targets of the m7G-cap binding protein LARP1. The expression of LARP1 targets and snoRNAs involved in ribosome biogenesis is selectively compromised in Rnmt cKO CD4 T cells resulting in decreased ribosome synthesis, reduced translation rates and proliferation failure. By enhancing ribosome abundance, upregulation of RNMT co-ordinates mRNA capping and processing with increased translational capacity during T cell activation.


Assuntos
Ativação Linfocitária , Metiltransferases/fisiologia , Biossíntese de Proteínas , Ribossomos/metabolismo , Linfócitos T/enzimologia , Animais , Técnicas de Inativação de Genes , Guanosina/metabolismo , Ativação Linfocitária/genética , Metiltransferases/biossíntese , Metiltransferases/genética , Camundongos , Capuzes de RNA/química , Capuzes de RNA/metabolismo , Processamento Pós-Transcricional do RNA , RNA Mensageiro/química , RNA Mensageiro/metabolismo , Pequeno RNA não Traduzido/metabolismo , Proteínas de Ligação a RNA/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Regulação para Cima
2.
Molecules ; 26(4)2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33671275

RESUMO

Oregano (Origanum vulgare L.) and thyme (Thymus vulgaris L.) have long been known for their organoleptic properties. Both plants are widely used in cuisine worldwide in fresh and dried form and as a pharmaceutical raw material. The study aimed to assess if the type of cultivation influenced chosen chemical parameters (total polyphenols by Folin-Ciocalteu method; carotenoids and chlorophyll content by Lichtenthaler method), antimicrobial activity (with chosen reference microbial strains) and shaped cytotoxicity (with L929 mouse fibroblasts cell line) in water macerates of dry oregano and thyme. Polyphenols content and antimicrobial activity were higher in water macerates obtained from conventional cultivation (independently from herb species), unlike the pigments in a higher amount in macerates from organic herbs cultivation. Among all tested macerates stronger antimicrobial properties (effective in inhibiting the growth of Pseudomonas aeruginosa, Bacillus cereus and Salmonella enteritidis) and higher cytotoxicity (abilities to diminish the growth of L929 fibroblasts cytotoxicity) characterized the conventionally cultivated thyme macerate.


Assuntos
Agricultura , Carotenoides/análise , Clorofila/análise , Fenóis/análise , Água/química , Animais , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular , Camundongos , Testes de Sensibilidade Microbiana , Origanum/química , Extratos Vegetais , Polifenóis/análise , Thymus (Planta)/química
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