Translation by ribosome shunting on adenovirus and hsp70 mRNAs facilitated by complementarity to 18S rRNA

Abstract

Translation initiation on eukaryotic mRNAs involves 40S ribosome association with mRNA caps (m7GpppN), mediated by initiation factor eIF4F. 40S eukaryotic ribosomes and initiation factors undergo 5' scanning to the initiation codon, with no known role for complementarity between eukaryotic 18S rRNA and the 5' noncoding region of mRNAs. We demonstrate that the 5' noncoding region of human adenovirus late mRNAs, known as the tripartite leader, utilizes a striking complementarity to 18S rRNA to facilitate a novel form of translation initiation referred to as ribosome shunting, in which 40S ribosomes bind the cap and bypass large segments of the mRNA to reach the initiation codon. Related elements are also shown to promote ribosome shunting in adenovirus IVa2 intermediate phase mRNA during virus infection and in human heat shock protein 70 (hsp70) mRNA for selective translation during heat shock. The importance of mRNA complementarity to 185 rRNA suggests that ribosome shunting may involve either specific RNA structural features or a prokaryotic-like interaction between mRNA and rRNA.