Translational Regulation of Gene Expression in Mycobacterium: A Means for Coordinating the Expression of Functionally Related Proteins

Mycobacterium tuberculosis (Mtb) is one of the world’s deadliest infectious agents. Consequently, a top priority has been to identify the mechanisms that Mtb uses to regulate the expression of genes involved in its virulence/persistence. Our over arching focus is on the translational regulation of gene expression. Our studies indicate that Mtb leverages differential codon usage and tRNA expression during both initiation and elongation to regulate protein synthesis. Translation initiation plays a key role in determining protein expression levels through its influence on the density of ribosomes bound on an mRNA. In bacteria, the initiation complex typically assembles with tRNAfMet bound to an AUG codon. However, sometimes the complex must assemble on a non-canonical GUG or UUG initiation codon. In Mtb, and in the model organism M. smegmatis (Msm) which we use for our experiments, approximately forty percent of the initiation codons are non-canonical. By contrast, non-canonical initiation codons are used in...