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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2018)

Translation initiation is a highly regulated process that plays a significant role in maintaining homeostasis. It has been shown to be a critical step in the proliferation of cancer and a crucial target for a variety of viruses. Thus, it has become an attractive target for the development of therapeutic drugs. Further knowledge of the mechanism of translation initiation might be beneficial in improving the efficiency of novel therapeutic drugs.

Though extensive work has been done to understand the mechanism in different species, studies of human translation initiation (specifically the eIF4E ● eIF4G1 ● PABP1 interactions) have been limited to cell-based assays and the use of small recombinant eIF4G1 variants.

Here we use a recombinant variant of eIF4G1 capable of interacting with both eIF4E and PABP1 to determine possible complex formations in the presence of different mRNAs. We find that complex formation is possible with a variety of mRNAs and in the presence or absence of the m7G cap or poly A tail. Furthermore, we demonstrate that eIF4G1 modulates eIF4E cap binding affinity and preferentially interacts with cap-bound eIF4E using a previously unidentified region. Finally, we show that eIF4G1 possess an additional RNA binding domain in its N-terminal region.

    Cover page: Bridging the Gap: Insights into the eIF4E-eIF4G1-PABP1-mRNA Complex
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2022)
    Influenza A virus (IAV) is a human-infecting pathogen with a history of causing seasonal epidemics and on several occasions worldwide pandemics. Infection by IAV causes a dramatic decrease in host mRNA translation, whereas viral mRNAs are efficiently translated. The IAV mRNAs have a highly conserved 5'-untranslated region (5'UTR) that is rich in adenosine residues. We show that the human polyadenylate binding protein 1 (PABP1) binds to the 5'UTR of the viral mRNAs. The interaction of PABP1 with the viral 5'UTR makes the translation of viral mRNAs more resistant to canonical cap-dependent translation inhibition than model mRNAs. Additionally, PABP1 bound to the viral 5'UTR can recruit eIF4G in an eIF4E-independent manner. These results indicate that PABP1 bound to the viral 5'UTR may promote eIF4E-independent translation initiation.
      Cover page: PABP1 Drives the Selective Translation of Influenza A Virus mRNA
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