Translational frameshifting

Acatalasemia is a rare hereditary deficiency of tissue catalase and is inherited as an autosomal recessive trait (03). This enzyme deficiency was discovered in 1948 by Takahara and Miyamoto (Tl). Two different types of acatalasemia can be distinguished clinically and biochemically. The severe form, Japanese-type acatalasemia, is characterized by nearly total loss of catalase activity in the red blood cells and is often associated with an ulcerating lesion of the oral cavity. The asymptomatic Swiss-type acatalasemia is characterized by residual catalase activity with aberrant biochemical properties. In four unrelated families with Japanese-type acatalasemia, a splicing mutation due to a G-to-A transition at the fifth nucleotide in intron 4 was elucidated (K20, W5). We have also determined a single base deletion resulting in the frameshift and premature translational termination in the Japanese patient (HI6). 

The answer is C. Production of a truncated protein indicates that a mutation has occurred, but this phenomenon may have arisen from a frameshift mutation (insertion or deletion) or by a nonsense mutation. The most likely possibility is a nonsense mutation because sequence analysis of the truncated protein showed that it had normal (wild-type) sequence. Insertion and deletion events often produce a stretch of garbled or abnormal protein sequence at the C-terminal end of the truncated protein arising from out-of-frame translation of the mRNA downstream of the mutation until a stop codon is encountered. 

Lee SI, Umen JG, Varmus HE (1995) A genetic screen identifies cellular factors involved in retroviral-1 frameshifting. Proc Natl Acad Sci USA 92 6587-6591 Leeds P, Peltz SW, Jacobson A, Culbertson MR (1991) The product of the yeast UPFl gene is required for rapid turnover of mRNAs containing a premature translational termination codon. Genes Dev 5 2303—... 

The effects of small changes to the base code such as base transitions and frameshift mutations are illustrated in Table 6.1. It can be seen that the consequences in translation vary with the particular change. 

The y subunit is encoded by a portion of the gene for the r subunit, such that the amino-terminal 66% of the t subunit has the same amino acid sequence as the y subunit, The y subunit is generated by a translational frameshifting mechanism (see... 

Changing Horses in Midstream Translational Frameshifting and mRNA Editing... 

The product of the pol gene (reverse transcriptase) is translated as a larger polyprotein, on the same mRNA that is used for the gag protein alone (see Fig. 26-30). The polyprotein, or gag-pol protein, is then trimmed to the mature reverse transcriptase by proteolytic digestion. Production of the polyprotein requires a translational frameshift in the overlap region to allow the ribosome to bypass the UAG termination codon at the end of the gag gene (shaded pink in Fig. 1). 

Frameshifts occur during about 5% of translations of this mRNA, and the gag-pol polyprotein (and ulti-... 

Klobutcher, L.A. Farabaugh, P.J. (2002) Shifty ciliates frequent programmed translational frameshifting in Euplotids. 

Most translation is terminated at this stop codon, but frameshifting, which is induced by a high polyamine concentration, allows read-through and synthesis of the antizyme protein. In rare cases frameshifting may lead to translational bypass of some codons on the mRNA. Such a case is found in a bacteriophage T4 mRNA for which the E. coli ribosomes bypass 50 nucleotides in order to complete the synthesis of a... 

Frameshift mutations. Insertions or deletions of genetic material that lead to a shift in the translation of the reading frame. The mutation usually leads to nonfunctional proteins. 

Although 10% of all PCR-generated variants contained frameshift mutations (leading to early termination of translation), the mutation frequency of 0.93 % on the nucleotide level yielded 1.78% amino acid substitutions after translation. Because multiple substitutions within a single codon are extremely rare, a proportion of 30% of all mutations were silent that is, they did not influence the amino acid sequence. 

Cobucci-Ponzano, B., Conte, F., Benelli, D., Londei, P., Flagiello, A., Monti, M., Pucci, P., Rossi, M. and Moracci, M. (2006). The gene of an archaeal alpha-L-fucosidase is expressed by translational frameshifting. Nucleic Acids Res, 34,4258-4268. 

The dehydratase gene drtrM from S. peucetius is located in the daunorubicin biosynthetic cluster. Although the gene was believed to be required for the synthesis of daunosamine, a frameshift in the DNA sequence was detected which causes premature termination of translation. Inactivation of dnrM did not prevent daunorubicin production. The data indicate that the product of a second dehydratase gene detected outside of the biosynthetic gene cluster is involved in the biosynthesis of daunomycin (29) [144]. 

Bjork GR, Wikstrom PM, Bystrom AS. lYevention of translational frameshifting by the modified nucleoside 1-methylguanosine. Science 1989 244 986-989. 

---