The eIF1A solution structure reveals a large RNA-binding surface importantfor scanning function

The translation initiation factor eIF1A is necessary for directing the 43S preinitiation complex from the 5' end of the mRNA to the initiation codon i n a process termed scanning. We have determined the solution structure of h uman eIF1A, which reveals an oligonucleotide-binding (OB) fold and an addit ional domain. NMR titration experiments showed that eIF1A binds single-stra nded RNA oligonucleotides in a site-specific, but non-sequence-specific man ner, hinting at an mRNA interaction rather than specific rRNA or tRNA bindi ng. The RNA binding surface extends over a large area covering the canonica l OB fold binding site as well as a groove leading to the second domain. Si te-directed mutations at multiple positions along the RNA-binding surface w ere defective in the ability to properly assemble preinitiation complexes a t the AUG codon in vitro.