RESUMEN
Prenatal lethality associated with mouse knockout of Mettl16, a recently identified RNA N6-methyladenosine (m6A) methyltransferase, has hampered characterization of the essential role of METTL16-mediated RNA m6A modification in early embryonic development. Here, using cross-species single-cell RNA sequencing analysis, we found that during early embryonic development, METTL16 is more highly expressed in vertebrate hematopoietic stem and progenitor cells (HSPCs) than other methyltransferases. In Mettl16-deficient zebrafish, proliferation capacity of embryonic HSPCs is compromised due to G1/S cell cycle arrest, an effect whose rescue requires Mettl16 with intact methyltransferase activity. We further identify the cell-cycle transcription factor mybl2b as a directly regulated by Mettl16-mediated m6A modification. Mettl16 deficiency resulted in the destabilization of mybl2b mRNA, likely due to lost binding by the m6A reader Igf2bp1 in vivo. Moreover, we found that the METTL16-m6A-MYBL2-IGF2BP1 axis controlling G1/S progression is conserved in humans. Collectively, our findings elucidate the critical function of METTL16-mediated m6A modification in HSPC cell cycle progression during early embryonic development.
Asunto(s)
Células Madre Hematopoyéticas , Metiltransferasas , Metilación de ARN , Proteínas de Unión al ARN , Factores de Transcripción , Pez Cebra , Animales , Humanos , Ratones , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/genética , Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proliferación Celular , Desarrollo Embrionario/genética , Regulación del Desarrollo de la Expresión Génica , Células Madre Hematopoyéticas/metabolismo , Células Madre Hematopoyéticas/citología , Metiltransferasas/metabolismo , Metiltransferasas/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Pez Cebra/metabolismo , Pez Cebra/embriología , Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Metilación de ARN/genéticaRESUMEN
Dendrobium nobile (D. nobile) is a valuable Chinese herbal medicine. The discovery of microbial resources from has provided a wealth of raw materials. Stalk rot, which is caused by Pestalotiopsis, is one of the most serious diseases of D nobile and has resulted in serious losses in production. However, an effective method for the prevention and control of stalk rot remains lacking. In this study, we aimed to identify a biocontrol strain against Pestalotiopsis. We isolated Paenibacillus polymyxa Y-1, an endophytic bacterium, from the stem of D. nobile. Three pairs of active metabolites isolated from this bacterium were identified as fusaricidin compounds. We then investigated the mechanism of fusaricidin compounds on Pestalotiopsis via proteomics. Proteomics data showed that the compounds mainly inhibit energy generation in the respiratory chain and amino acid biosynthesis of Pestalotiopsis.