Protein Mis-Termination Initiates Genetic Diseases, Cancers, and Restricts Bacterial Genome Expansion

Abstract

Protein termination is an important cellular process. Protein termination relies on the stop-codons in the mRNA interacting properly with the releasing factors on the ribosome. One third of inherited diseases, including cancers, are associated with the mutation of the stop-codons. Many pathogens and viruses are able to manipulate their stop-codons to express their virulence. The influence of stop-codons is not limited to the primary reading frame of the genes. Stop-codons in the second and third reading frames are referred as premature stop signals (PSC). Stop-codons and PSCs together are collectively referred as stop-signals. The ratios of the stop-signals (referred as translation stop-signals ratio or TSSR) of genetically related bacteria, despite their great differences in gene contents, are much alike. This nearly identical Genomic-TSSR value of genetically related bacteria may suggest that bacterial genome expansion is limited by their unique stop-signals bias. We review the protein termination process and the different types of stop-codon mutation in plants, animals, microbes, and viruses, with special emphasis on the role of PSCs in directing bacterial evolution in their natural environments. Knowing the limit of genomic boundary could facilitate the formulation of new strategies in controlling the spread of diseases and combat antibiotic-resistant bacteria.