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

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/261776 doi: bioRxiv preprint complexing with IFIT3 reproducibly decreased the concentration of IFIT1 required to cause 50 % inhibition of the same reporter ( Figure 3C ). IFIT1 inhibited translation of the cap0-ZV reporter less than the -globin reporter overall, but complexing with IFIT3 again enhanced IFIT1's translation inhibitory effect ( Figure 3D ). Because the heterotetrameric IFIT1:IFIT2:IFIT3 complex was unstable we focused on the heterotrimeric complex for further analysis. As can be seen in Figure 3E and 3F, stimulation of IFIT1 translation inhibition was reproducibly observed in the context of the IFIT1:IFIT2:IFIT3 complex. Reporter mRNAs bearing cap1 structures were also examined ( Figure 3C -F and Figure S4 ). Inhibition of cap1 mRNAs was only observed at very high concentrations of IFIT1.