Molecular biology: Structural roles for human translation factor elF3 in initiation of protein synthesis

Protein synthesis in mammalian cells requires initiation factor elF3, a ∼750-kilodalton complex that controls assembly of 40S ribosomal subunits on messenger RNAs (mRNAs) bearing either a 5′-cap or an internal ribosome entry site (IRES). Cryo-electron microscopy reconstructions show that elF3, a five-lobed particle, interacts with the hepatitis C virus (HCV) IRES RNA and the 5′-cap binding complex elF4F via the same domain. Detailed modeling of elF3 and elF4F onto the 40S ribosomal subunit reveals that elF3 uses elF4F or the HCV IRES in structurally similar ways to position the mRNA strand near the exit site of 40S, promoting initiation complex assembly.