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
A metal-free (NH4)2S2O8-mediated decarboxylative trifluoromethylation reaction of alkenes with 3,3,3-trifluoro-2,2-dimethylpropionic acid has been proposed. This method offers a novel route for the direct synthesis of a series of CMe2CF3-containing quinazolinones from basic chemical raw materials. The reaction mechanism was studied by a radical trapping test and DFT methods, verifying an oxidation-triggered cascade process promoted by the CMe2CF3 radicals. This strategy provides advantages such as high yield, wide substrate compatibility, and high atom economy.
RESUMEN
A novel cascade radical addition/cyclization reaction of non-activated olefins and oxamic acids has been proposed. Under transition metal-free conditions, 36 quinazolinone derivatives containing an amide moiety were successfully synthesized, with the highest yield being 81%. This method involves the preparation of aminoacyl fused quinazolinone derivatives under mild conditions, offering advantages such as a high yield, a broad substrate compatibility, and a high atom economy.
RESUMEN
Rationally switching reactive oxygen species (ROS) reactions in advanced oxidation processes (AOPs) is urgently needed to improve the adaptability and efficiency for the engineering application. Herein we synthesized bimetallic Mn-Pt catalysts based on zeolite to realize the switching of ROS reactions in catalytic ozonation for sustainable degradation of organic pollutants from water. The ROS reactions switched from singlet oxygen (1O2, 71.01%) to radical-dominated (93.79%) pathway by simply introducing defects and changing Pt/Mn ratios. The oxygen vacancy induced by anchoring Mn-Pt species from zeolite external surface (MnPt/H-Beta) to internal framework (MnPt@Si-Beta) exposes more electron-rich Pt2+/Pt4+ redox sites, accelerating the decomposition of O3 to generate â¢OH via electron transfer and switching ROS reactions. The Mn site acted as a bridge plays a critical role in conducting electrons from organic pollutants to Pt sites, which solidly solves the electron loss of catalysts, facilitating the efficient degradation of pollutants. A 34.7-fold increase in phenol degradation compared with the non-catalytic ozonation and an excellent catalytic stability are achieved by MnPt@Si-Beta/O3. The 1O2-dominated ROS reaction originated from MnPt/H-Beta/O3 exhibits superior performances in anti-interference for Cl-, HCO3-, NO3-, and SO4-. This work establishes a novel strategy for switching ROS reactions to expand the targeted applications of O3 based AOPs for environmental remediation.