IFIT3 and IFIT2/3 promote IFIT1-mediated translation inhibition by enhancing binding to non-self RNA

Renata C Fleith; Harriet V Mears; Edward Emmott; Stephen C Graham; Daniel S Mansur; Trevor R Sweeney

It is possible that the RNA binding surface of IFIT1 may be extended by interaction with its binding partners. This has the potential to expand the repertoire of RNAs IFIT1 can interact with by providing additional stabilising interactions. Moreover, it is unclear why inclusion of IFIT3 alone has a stronger effect on translation inhibition than inclusion of the IFIT2:IFIT3 heterodimer. Since inclusion of IFIT2 alone had no impact on the translation inhibition activity of IFIT1 it is possible that the stimulatory effect is a result of the IFIT3 in the IFIT2:IFIT3 complex. The physiological role for this stimulation of binding is not immediately clear as we have previously demonstrated that IFIT1 binding to cap0-mRNA is sufficient to prevent association of the cap-binding translation initiation factor, eIF4F, in vitro (13) . However, a requirement for co-expression of other IFITs for the full anti-viral activity of IFIT1 has been reported (12) . During infection the enhanced binding of IFIT1, as a result of author/funder. All rights reserved. No reuse allowed without permission.