Cap-Dependent vs. Cap-Independent Translation

Our understanding of gene expression has come far since the ‘one-gene one-polypeptide’ hypothesis proposed by Beadle and Tatum. At the Gomez lab we address the gradual recognition that a growing number of polycistronic genes, originally discovered in viruses, are being identified within the mammalian genome, and that these may provide new insights into disease mechanisms and treatment.  Although the canonical mechanism of translation initiation has been studied extensively, here we highlight a process of noncanonical translation, that is a growing source for understanding complex inheritance, the elucidation of disease mechanisms, and the discovery of novel therapeutic targets. Identification of additional polycistronic genes may provide new insights into disease therapy and allow for new discoveries of both translational and disease mechanisms.

Read more about our interest in alternative translation in our review

Exclusionary Tests to Determine Non-Canonical Translation

In addition to evidence supporting IRES activity, strict exclusionary criteria have to be established to show that protein cleavage, alternative splicing, cryptic promoter, or other phenomena are not responsible for the second protein production.

Careful analysis of the exact sequence and structure of putative IRES and the start amino acid of the secondary protein must be determined in its native context for further experimentation.