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Overexpression of RbfA in the absence of the KsgA checkpoint results in impaired translation initiation.

ABSTRACT: KsgA, a universally conserved small ribosomal subunit (SSU) rRNA methyltransferase, has recently been shown to facilitate a checkpoint within the ribosome maturation pathway. Under standard growth conditions removal of the KsgA checkpoint has a subtle impact on cell growth; yet, upon overexpresssion of RbfA, a ribosome maturation factor, KsgA becomes essential. Our results demonstrate the requirement of KsgA, in the presence of excess RbfA, both for the incorporation of ribosomal protein S21 to the developing SSU, and for final maturation of SSU rRNA. Also, when SSU biogenesis is perturbed by an imbalance in KsgA and RbfA, a population of 70S-like particles accumulates that is compositionally, functionally and structurally distinct from mature 70S ribosomes. Thus, our work suggests that KsgA and RbfA function together and are required for SSU maturation, and that additional checkpoints likely act to modulate malfunctional 70S particle formation in vivo.

SUBMITTER: Connolly K

PROVIDER: S-EPMC3583373 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Overexpression of RbfA in the absence of the KsgA checkpoint results in impaired translation initiation.

Connolly Keith K Culver Gloria G

Molecular microbiology 20130206 5

KsgA, a universally conserved small ribosomal subunit (SSU) rRNA methyltransferase, has recently been shown to facilitate a checkpoint within the ribosome maturation pathway. Under standard growth conditions removal of the KsgA checkpoint has a subtle impact on cell growth; yet, upon overexpresssion of RbfA, a ribosome maturation factor, KsgA becomes essential. Our results demonstrate the requirement of KsgA, in the presence of excess RbfA, both for the incorporation of ribosomal protein S21 to ...[more]

PMID: 23387871

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Project description:Eukaryotic translation initiation factor 5A2 (EIF5A2) plays an important role in tumor progression and prognosis evaluation. However, little information is available about its potential role in gastric cancer. This study aimed to investigate the function of EIF5A2 in tumor progression and its potential mechanisms. EIF5A2 expression was measured in human gastric cancer cell lines, the immortalized gastric mucosal epithelial cell line (GES-1) and human gastric cancer tissues and knocked down by RNA interference or upregulated by EIF5A2 plasmid transfection. Cell proliferation, migration and invasion were assessed in vitro. The downstream targets of EIF5A2 were examined by western blotting. EIF5A2 and its potential target metastasis-associated protein 1 (MTA1) expression were examined in 160 pairs of human gastric cancer and adjacent non-tumor specimens using immunohistochemistry (IHC) staining, and its correlation with clinicopathological features and survival was investigated. Knockdown of EIF5A2 or MTA1 caused an apparent suppression of HGC27 cell proliferation, migration and invasion. After knockdown of EIF5A2 in HGC27 cells, E-cadherin levels were upregulated and vimentin, cyclin D1, cyclin D3, C-MYC and MTA1 levels were downregulated. Upregulation of EIF5A2 in MKN45 cells resulted in the converse. IHC results showed a positive correlation between EIF5A2 and MTA1 expression in gastric cancers (P<0.001). Both EIF5A2 and MTA1 overexpression were correlated with pT stage (P=0.018 and P=0.042), pN stage (P=0.037 and P=0.020) and lymphovascular invasion (P=0.016 and P=0.044). EIF5A2 or MTA1 overexpression was significantly associated with poor overall survival and disease-free survival (All P<0.05). Multivariate analyses identified EIF5A2 as an independent predictor for both overall survival (P=0.012) and disease-free survival (P=0.008) in gastric cancer patients. Our findings indicate that EIF5A2 upregulation plays an important oncogenic role in gastric cancer. EIF5A2 may represent a new predictor for poor survival and is a potential therapeutic target for gastric cancer.

Dataset Information

Overexpression of RbfA in the absence of the KsgA checkpoint results in impaired translation initiation.

Publications

Overexpression of RbfA in the absence of the KsgA checkpoint results in impaired translation initiation.

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