Cep57 regulates human centrosomes through multivalent interactions.

Human Cep57 is a coiled-coil scaffold at the pericentriolar matrix (PCM), controlling centriole duplication and centrosome maturation for faithful cell division. Genetic truncation mutations of Cep57 are associated with the mosaic-variegated aneuploidy (MVA) syndrome. During interphase, Cep57 forms a complex with Cep63 and Cep152, serving as regulators for centrosome maturation. However, the molecular interplay of Cep57 with these essential scaffolding proteins remains unclear. Here, we demonstrate that Cep57 undergoes liquid-liquid phase separation (LLPS) driven by three critical domains (NTD, CTD, and polybasic LMN). In vitro Cep57 condensates catalyze microtubule nucleation via the LMN motif-mediated tubulin concentration. In cells, the LMN motif is required for centrosomal microtubule aster formation. Moreover, Cep63 restricts Cep57 assembly, expansion, and microtubule polymerization activity. Overexpression of competitive constructs for multivalent interactions, including an MVA mutation, leads to excessive centrosome duplication. In Cep57-depleted cells, self-assembly mutants failed to rescue centriole disengagement and PCM disorganization. Thus, Cep57's multivalent interactions are pivotal for maintaining the accurate structural and functional integrity of human centrosomes.

Systematic Studies on the Anti-SARS-CoV-2 Mechanisms of Tea Polyphenol-Related Natural Products.

The causative pathogen of COVID-19, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), utilizes the receptor-binding domain (RBD) of the spike protein to bind to human receptor angiotensin-converting enzyme 2 (ACE2). Further cleavage of spike by human proteases furin, TMPRSS2, and/or cathepsin L facilitates viral entry into the host cells for replication, where the maturation of polyproteins by 3C-like protease (3CLpro) and papain-like protease (PLpro) yields functional nonstructural proteins (NSPs) such as RNA-dependent RNA polymerase (RdRp) to synthesize mRNA of structural proteins. By testing the tea polyphenol-related natural products through various assays, we found that the active antivirals prevented SARS-CoV-2 entry by blocking the RBD/ACE2 interaction and inhibiting the relevant human proteases, although some also inhibited the viral enzymes essential for replication. Due to their multitargeting properties, these compounds were often misinterpreted for their antiviral mechanisms. In this study, we provide a systematic protocol to check and clarify their anti-SARS-CoV-2 mechanisms, which should be applicable for all of the antivirals.

Development of a Novel Endometrial Signature Based on Endometrial microRNA for Determining the Optimal Timing for Embryo Transfer.

Though tremendous advances have been made in the field of in vitro fertilization (IVF), a portion of patients are still affected by embryo implantation failure issues. One of the most significant factors contributing to implantation failure is a uterine condition called displaced window of implantation (WOI), which refers to an unsynchronized endometrium and embryo transfer time for IVF patients. Previous studies have shown that microRNAs (miRNAs) can be important biomarkers in the reproductive process. In this study, we aim to develop a miRNA-based classifier to identify the WOI for optimal time for embryo transfer. A reproductive-related PanelChip® was used to obtain the miRNA expression profiles from the 200 patients who underwent IVF treatment. In total, 143 out of the 167 miRNAs with amplification signals across 90% of the expression profiles were utilized to build a miRNA-based classifier. The microRNA-based classifier identified the optimal timing for embryo transfer with an accuracy of 93.9%, a sensitivity of 85.3%, and a specificity of 92.4% in the training set, and an accuracy of 88.5% in the testing set, showing high promise in accurately identifying the WOI for the optimal timing for embryo transfer.