Nucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells

The robust proliferation of cancer cells requires vastly elevated levels of protein synthesis, which relies on a steady supply of aminoacylated tRNAs. Delivery of tRNAs to the cytoplasm is a highly regulated process, but the machinery for tRNA nuclear export is not fully elucidated. In this study, using a live cell imaging strategy that visualizes nascent transcripts from a specific tRNA gene in yeast, we identified the nuclear basket proteins Mlp1 and Mlp2, two homologs of the human TPR protein, as regulators of tRNA export. TPR expression is significantly increased in lung cancer tissues and correlated with poor prognosis. Consistently, knockdown of TPR inhibits tRNA nuclear export, protein synthesis and cell growth in lung cancer cell lines. We further show that NXF1, a well-known mRNA nuclear export factor, associates with tRNAs and mediates their transport through nuclear pores. Collectively, our findings uncover a conserved mechanism that regulates nuclear export of tRNAs, which is a limiting step in protein synthesis in eukaryotes.

Identification of biomarkers and signaling pathways during the treatment of multiple myeloma

Multiple myeloma (MM) is an incurable hematologic malignancy, which is characterized by increased bone marrow plasma cells, osteolytic lesions, and anemia. Here, our aim is to characterize significant biomarkers and signaling pathways during the treatment of MM by using bioinformatic methods. The GSE180018 dataset was generated by DNBSEQ-G400 (Homo sapiens). The KEGG and GO analyses showed the biological processes such as " Protein export”, “Protein processing in endoplasmic reticulum”, “Vibrio cholerae infection”, “Fc gamma R-mediated phagocytosis" are mainly affected in FOXM1 KO MM cells. Moreover, we identified the significant genes including CD44, NOTCH1, SELL, RAC2, HSPA8, VAV1, DDIT3, PLK1, HYOU1, ITGAL in FOXM1 KO MM cells. Therefore, our study may provide further guidance for the drug development of MM.

SecA – a multidomain and multitask bacterial export protein

Most bacterial secretory proteins destined to the extracytoplasmic space are secreted posttranslationally by the Sec translocase. SecA, a key component of the Sec system, is the ATPase motor protein, directly responsible for transferring the preprotein across the cytoplasmic membrane. SecA is a large protein, composed of several domains, capable of binding client preproteins and a variety of partners, including the SecYEG inner membrane channel complex, membrane phospholipids and ribosomes. SecA-mediated translocation can be divided into two major steps: (1) targeting of the preproteins to the membrane translocation apparatus and (2) transport across the membrane through the SecYEG channel. In this review we present current knowledge regarding SecA structure and function of this protein in both translocation steps. The most recent model of the SecA-dependent preprotein mechanical translocation across the bacterial cytoplasmic membrane is described. A possibility of targeting SecA with inhibitory compounds as a strategy to combat pathogenic bacteria will be discussed as well.

Interaction of Nuclear Export Protein with G Protein Pathway Suppressor 2 (GPS2) Facilitates Influenza A Virus Replication by Weakening the Inhibition of GPS2 to RNA Synthesis and Ribonucleoprotein Assembly

ABSTRACT The nuclear export protein (NEP) serves multiple functions in the life cycle of influenza A virus (IAV). Identifying novel host proteins that interact with NEP and understanding their functions in IAV replication are of great interest. In this study, we screened and confirmed the direct interaction of G protein pathway suppressor 2 (GPS2) with NEP through a yeast two-hybrid screening assay and glutathione S-transferase pulldown and coimmunoprecipitation assays. Knockdown or knockout of GPS2 enhanced IAV titers, whereas overexpression of GPS2 impaired IAV replication, demonstrating that GPS2 acted as a negative host factor in IAV replication. Meanwhile, GPS2 inhibited viral RNA synthesis by reducing the assembly of IAV polymerase. Interestingly, IAV NEP interacted with GPS2 and mediated its nuclear export, thereby activating the degradation of GPS2. Thus, NEP-GPS2 interaction weakened the inhibition of GPS2 to viral polymerase activity and benefited virus replication. Overall, this study identified the novel NEP-binding host partner GPS2 as a critical host factor to participate in IAV replication. These findings provided novel insights into the interactions between IAV and host cells, revealing a new function for GPS2 during IAV replication. IMPORTANCE NEP is proposed to play multiple biologically important roles in the life cycle of IAV, which largely relies on host factors by interaction. Our study demonstrated that GPS2 could reduce the interaction between polymerase basic 1 (PB1) and PB2 and interfere with viral ribonucleoprotein (vRNP) assembly. Thus, GPS2 inhibited the RNA synthesis of IAV and negatively regulated its replication. Importantly, IAV NEP interacted with GPS2 and mediated the nuclear export of GPS2, thereby activating the degradation of GPS2. Thus, NEP-GPS2 interaction weakened the inhibition of GPS2 to viral polymerase activity and benefited virus replication.