UC San Diego

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.