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Sean Alemi
Hepatitis C virus (HCV) infects about 170 million people
worldwide. A critical aspect of the virus's ability to infect
the host is its efficiency in using the human translation
machinery to synthesize its own proteins. The HCV mRNA does
this by using an internal ribosomal entry site (IRES) - one
of the most conserved regions of the HCV genome - rather than
cap dependent initiation, potentially freeing it from normal
cellular regulation. In addition to binding the 40S ribosome,
the HCV IRES specifically binds to and requires human translation
initiation factor eiF3.
Cryo-electron microscopy models suggest that there is a large
surface of interaction between the HCV IRES and eIF3, but the
details of this interaction are mostly unknown. The IIIabc
region of the IRES is thought to be especially important, and is
the focus of much of my efforts. By incorporating 4-thio-uridine,
a nucleotide that will cross link in the presence of long wave
UV light, I aim to create a transcript that can be covalently
linked to the eIF3 protein complex. The ultimate goal of these
efforts is to clarify which of the 13 subunits of eIF3 the HCV
RNA interacts with.
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