Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use

Atkins, John F.; Loughran, Gary; Bhatt, Pramod R.; Firth, Andrew E.; Baranov, Pavel V.

Cyanobacteria, considered to be the most abundant photosynthetic organisms (313) , and some chemolithoautotrophic bacteria, employ a carbon dioxide concentrating mechanism to overcome the low affinity of the key enzyme, Ribulose-1,5-bisphosphate Carboxylase/Oxygenase (RuBisCO), for CO 2 and promiscuous activity for competing O 2 substrate. A key part of the concentrating mechanism is giant organelle-like structures, carboxysomes, of 200+ MDa and 80-500 nm that contain thousands of protomers, and which have some resemblance to icosahedral viral capsids. RuBisCO is sequestered within the protein shell microcompartment. Remarkably just 10 genes from Halothiobacillus neapolitanus are sufficient to express the ␣carboxysome in the heterologous bacterium E. coli (314) . One of these genes encodes the cargo proteins carbonic anhydrase and several encode shell proteins. Decoding of one of the genes, csoS2, required for carboxysome formation (315), utilizes 50% efficient −1 frameshifting (316). The product of standard decoding, Cso2B, is 869 amino acids and the product of frameshifting, Cso2A has 570 amino acids with its 3 C-terminal amino acids encoded by the −1 frame. Unlike Cso2B it cannot function in forming carboxysome. It has been speculated that the function of having two forms of Cso2 is related to partitioning of Ru-BisCO, Cso2B functioning primarily underneath the shell and Cso2A within the lumen of the carboxysome. But as Cso2B has only just been discovered, characterization will take some time. However, interestingly Cso2 has functional similarities to foot-and-mouth disease virus protein VP4 which binds to the interior side of the viral capsid (316). Currently 162 species are known with cso2 genes and 79 are predicted to utilize frameshifting (316), which is therefore important for the global carbon cycle. dnaX and the 1:1 ratio DNA polymerase products produced by alternative means