Yun Wei | Search PubMed

PubMed2026

Decoding sequence recognition code of nucleic acid-binding proteins of human-infecting DNA viruses.

Human-infecting DNA viruses remain major health threats, yet the DNA-recognition mechanisms of their nucleic acid-binding proteins (NBPs) are poorly understood. Here, we systematically profiled 103 viral NBPs from human-infecting DNA viruses, with three NBPs from non-human-infecting DNA viruses as controls, using high-throughput screening. This analysis identified diverse DNA-binding motifs and specificity modules, including convergent recognition of a conserved CCACC motif across phylogenetically distant viruses. Notably, viral NBP binding-site distributions varied with genome size, and several NBPs from small-genome viruses showed enrichment on mitochondrial DNA. Functional assays further supported their mitochondrial association and effects on mitochondrial membrane potential. By integrating an ivTRT-based ssDNA-SELEX workflow, we further found that ssDNA viral NBPs recognize dimer-like and inverted-repeat sequences with potential to form stem-loop structures. Collectively, this study constructs a comprehensive viral NBP DNA-recognition atlas, offering a fundamental resource for elucidating viral genome recognition mechanisms, virus-mitochondria interactions, and developing future antiviral strategies.

Letter↗

PubMed2024

The causal relationship between genetically predicted blood metabolites and idiopathic pulmonary fibrosis: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: Numerous metabolomic studies have confirmed the pivotal role of metabolic abnormalities in the development of idiopathic pulmonary fibrosis (IPF). Nevertheless, there is a lack of evidence on the causal relationship between circulating metabolites and the risk of IPF. METHODS: The potential causality between 486 blood metabolites and IPF was determined through a bidirectional two-sample Mendelian randomization (TSMR) analysis. A genome-wide association study (GWAS) involving 7,824 participants was performed to analyze metabolite data, and a GWAS meta-analysis involving 6,257 IPF cases and 947,616 control European subjects was conducted to analyze IPF data. The TSMR analysis was performed primarily with the inverse variance weighted model, supplemented by weighted mode, MR-Egger regression, and weighted median estimators. A battery of sensitivity analyses was performed, including horizontal pleiotropy assessment, heterogeneity test, Steiger test, and leave-one-out analysis. Furthermore, replication analysis and meta-analysis were conducted with another GWAS dataset of IPF containing 4,125 IPF cases and 20,464 control subjects. Mediation analyses were used to identify the mediating role of confounders in the effect of metabolites on IPF. RESULTS: There were four metabolites associated with the elevated risk of IPF, namely glucose (odds ratio [OR] = 2.49, 95% confidence interval [95%CI] = 1.13-5.49, P = 0.024), urea (OR = 6.24, 95% CI = 1.77-22.02, P = 0.004), guanosine (OR = 1.57, 95%CI = 1.07-2.30, P = 0.021), and ADpSGEGDFXAEGGGVR (OR = 1.70, 95%CI = 1.00-2.88, P = 0.0496). Of note, the effect of guanosine on IPF was found to be mediated by gastroesophageal reflux disease. Reverse Mendelian randomization analysis displayed that IPF might slightly elevate guanosine levels in the blood. CONCLUSION: Conclusively, hyperglycemia may confer a promoting effect on IPF, highlighting that attention should be paid to the relationship between diabetes and IPF, not solely to the diagnosis of diabetes. Additionally, urea, guanosine, and ADpSGEGDFXAEGGGVR also facilitate the development of IPF. This study may provide a reference for analyzing the potential mechanism of IPF and carry implications for the prevention and treatment of IPF.

Humans↗