Ribosomal tethering and clustering as mechanisms for translation initiation.

Eukaryotic mRNAs often recruit ribosomal subunits some distance upstream of the initiation codon; however, the mechanisms by which they reach the initiation codon remain to be fully elucidated. Although scanning is a widely accepted model, evidence for alternative mechanisms has accumulated. We previously suggested that this process may involve tethering of ribosomal complexes to the mRNA, in which the intervening mRNA is bypassed, or clustering, in which the initiation codon is reached by dynamic binding and release of ribosomal subunits at internal sites. The present studies tested the feasibility of these ideas by using model mRNAs and revealed that translation efficiency varied with the distance between the site of ribosomal recruitment and the initiation codon. The present studies also showed that translation could initiate efficiently at AUG codons located upstream of an internal site. These observations are consistent with ribosomal tethering at the cap structure and clustering at internal sites.