Highlights d 11 neutralizing antibodies against SARS-CoV-2 target three main epitopes on RBD d Epitope-A antibody 414-1 shows neutralizing IC 50 at 1.75 nM d Epitope-B antibody 553-15 can enhance the neutralizing abilities of other antibodies d One neutralizing antibody, 515-5, can cross neutralize SARS-CoV pseudovirus

Highlights d METTL5 shows strong substrate preference to 18S rRNA m 6 A1832 motif UAACA d The m 6 A1832 modification may affect decoding center in favoring mRNA binding d METTL5 promotes translation initiation, S6K activation, and breast cancer cell growth d C. elegans METL-5 regulates stress response, lifespan, and UPR ER

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The coronavirus induced disease 19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a worldwide threat to human lives, and neutralization antibodies present a great therapeutic potential in curing affected patients. We purified more than one thousand memory B cells specific to SARS-CoV-2 recombinant S1 or RBD antigens from 11 convalescent COVID-19 patients, and a total of 729 naturally paired heavy and light chain fragments were obtained by single B cell cloning technology. Among these, 178 recombinant monoclonal antibodies were tested positive for antigen binding, and 17 strong binders to S1 or RBD were identified with Kd(EC50) below 1 nM. Importantly, 12 antibodies could block pseudoviral entry into HEK293T cells overexpressing ACE2, with the best ones showing IC50 around 2-3 nM. From these 12 antibodies, we had tested two in authentic virus infection assay, and found one was able to effectively block live viral entry with IC50 around or below 15 nM. Interestingly, we also found a substantial portion of these antibodies crossreacting with the SARS-CoV spike protein.Altogether, our study provided potent neutralization antibodies as clinical therapeutics candidates for further development.

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RNF214 is an understudied ubiquitin ligase without any knowledge of its biological functions or specific protein substrates. Using an APEX2-mediated proximity labeling method coupled with the mass spectrometry technique, we identified the TEAD transcription factors in the Hippo pathway as interactors of RNF214. We showed that RNF214 induces non-proteolytic ubiquitylation at a conserved single lysine residue of TEADs, enhances the interactions between TEADs and the transcription coactivators of the Hippo pathway including YAP and TAZ, and then promotes transactivation of the downstream genes of the Hippo signaling. Moreover, we proved that YAP and TAZ could bind polyubiquitin chains, implying the underlying mechanisms by which RNF214 regulates the Hippo pathway. Furthermore, we found that RNF214 is overexpressed in hepatocellular carcinoma (HCC). Clinical and statistical analysis indicated that high expression levels of RNF214 are associated with low differentiation status and poor prognosis of HCC. Consistently, we showcased that RNF214 promotes proliferation, migration and invasion of HCC cells and HCC tumorigenesis in mouse models via the Hippo pathway. Collectively, our data revealed that RNF214 is a critical component in the Hippo pathway by forming a new signaling axis of RNF214-TEAD-YAP, thereby upregulating the transcriptional activities of the YAP/TAZ-TEAD complex. More importantly, our results suggest that RNF214 serves as an oncogene of HCC and could be a potential drug target of HCC therapy.