AUGmenting the proteome: Novel initiation codons and their role in protein isoform generation

As the field of molecular biology developed, and the understanding of how inherited genetic material results in the expression of proteins was established, the initial hypothesis was that one gene gave rise to one protein1. As researchers delved deeper into the organization of the genetic code and advances in messenger RNA (mRNA) and protein sequencing were subsequently made, it has become abundantly clear that multiple mechanisms exist meaning that many mRNAs encode more than one version of a protein. Although alternative promoters and alternative splicing play a considerable role in the generation of protein isoforms, in this article we discuss how usage of alternative translation initiation codons in eukaryotes can also lead to an expanded proteome.