ABSTRACT
Since December 2019, Wuhan city of Hubei Province has been the center of a number of patients infected with coronavirus disease 2019 (COVID-19). People are susceptible to be infected. The infection has spread to newborn and small infants, and severe cases of children have now occurred. Cases of infection in children have drawn great attention from the society. The pathogenesis of COVID-19 is unclear, and there is no specific drug for treatment, which brings great difficulties to epidemic prevention and clinical treatment. In this paper, we try to understand COVID-19 in children from different perspectives of TCM and western medicine. We also try to analyze the etiology, epidemic characteristics, disease development characteristics and treatment measures of COVID-19 in children. At the same time, we try to explore the etiology, pathogenesis, syndrome differentiation and treatment of COVID-19 in children with TCM. It is hoped that the combination of TCM and western medicine can better understand the new coronavirus pneumonia in children and its pathological basis, analyze the current trend of the epidemic situation, so as to find out safe and effective prevention and control measures and provide reference for clinical prevention and treatment of COVID-19 in children.
ABSTRACT
N-methyladenosine (mA), a ubiquitous RNA modification, is installed by METTL3-METTL14 complex. The structure of the heterodimeric complex between the methyltransferase domains (MTDs) of METTL3 and METTL14 has been previously determined. However, the MTDs alone possess no enzymatic activity. Here we present the solution structure for the zinc finger domain (ZFD) of METTL3, the inclusion of which fulfills the methyltransferase activity of METTL3-METTL14. We show that the ZFD specifically binds to an RNA containing 5'-GGACU-3' consensus sequence, but does not to one without. The ZFD thus serves as the target recognition domain, a structural feature previously shown for DNA methyltransferases, and cooperates with the MTDs of METTL3-METTL14 for catalysis. However, the interaction between the ZFD and the specific RNA is extremely weak, with the binding affinity at several hundred micromolar under physiological conditions. The ZFD contains two CCCH-type zinc fingers connected by an anti-parallel β-sheet. Mutational analysis and NMR titrations have mapped the functional interface to a contiguous surface. As a division of labor, the RNA-binding interface comprises basic residues from zinc finger 1 and hydrophobic residues from β-sheet and zinc finger 2. Further we show that the linker between the ZFD and MTD of METTL3 is flexible but partially folded, which may permit the cooperation between the two domains during catalysis. Together, the structural characterization of METTL3 ZFD paves the way to elucidate the atomic details of the entire process of RNA mA modification.