Human CNOT6L/CCR4, a member of the endonuclease-exonuclease-phosphatase (EEP) family enzymes, is one of the two deadenylase enzymes in the conserved CCR4-NOT complex. Here, we report inhibitor-bound crystal structures of the human CNOT6L nuclease domain in complex with the nucleotide CMP and the aminoglycoside neomycin. Deadenylase activity assays show that nucleotides are effective inhibitors of both CNOT6L and CNOT7, with AMP more effective than other nucleotides, and that neomycin is a weak deadenylase inhibitor. Structural analysis shows that all inhibitors occupy the substrate and magnesium-binding sites of CNOT6L, suggesting that inhibitors compete with both substrate and divalent magnesium ions for overlapping binding sites.

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Glioblastoma (GBM) is the most frequently identified malignancy of the brain. Due to the special tumor location, it is extremely urgent to explore key genes involved in the pathogenesis of GBM. In this study, we tried to identify vital genes that participate in the GBM progression by analyzing TCGA-sourced transcriptome data and identified 3183 differentially expressed genes (DEGs). Meanwhile, we also observed that CRYGN, MICAL2, BICDL1, PLK2, MTHFD2, OSMR, COL22A1, MSTN, and G0S2 expressions were significantly associated with patients’ survival. Immune infiltration analysis indicated that eight genes enhanced the immune infiltration in GBM, while BICDL1 had no significant effect. In conclusion, our study demonstrates that the eight genes are potential key genes involved in GBM and significantly connected to patients’ prognosis.