Aug Aaa Agc Uua Ggg Uau Cuu Uag Cua Cgg Ggc

The frequency of this hopping over six nucleotides (+6 shift) was only 1 %. Similar low-frequency hops over 2 to 9 nucleotides can be observed also within coding regions of mRNA. Specific mutations of tRNAs or ribosomes may increase the frequency of hopping up to 20 % or more.

The discovery of a hop over 50 nucleotides during translation of bacteriophage T4 DNA topoisomerase mRNA (gene 60 transcript) was a kind of sensation (Huang et al., 1988). In this case the translating ribosome with peptidyl-tRNAGly jumps from GGA codon at positions 136-138 to an identical codon 50 nucleotides downstream (Fig. 12.10). The efficiency of the jump is close to 100 %. A special structure of the 50-nucleotide section is required for efficiently skipping it. Essential elements of this structure are a stop codon 3'-adjacent to the take-off glycine codon, an extremely stable hairpin with tetraloop at the take-off site, and a proper size of the skipped section. In addition, a stretch of the nascent peptide (14 amino acid residues away from the peptidyl transferase center) is found to contribute to the efficiency of the hop. It is likely that the pausing at the stop codon and the subsequent stable hairpin provokes the taking-off, and the ribosome slips over the structured gap as a bulge without its melting. The taking-off, the bypassing of a stretch and the landing of the ribosome at a new, downstream codon can be considered as reprogrammed genetic decoding, or recoding of the message (Gesteland et al., 1992).

Another striking example of ribosome hoping is the case of translation of E. coli trpR mRNA (Benhar & Engelberg-Kulka, 1993). The E. coli trpR gene codes for the Trp repressor, a 12 kDa protein that regulates transcription of several operons and genes involved in tryptophan metabolism and transport. It has been observed that along with the main product of translation, some amount of a shorter protein, of about 10 kDa, is synthesized during translation of the same mRNA. The N-terminal part of the shorter protein is identical to that of the repressor, but the C-terminal part has been found to be completely different. It has proven that during translation, at a specific site of the mRNA, ribosomes occasionally (with a frequency of about 5 %) jump over an mRNA segment of 55 nucleotides in length, thus resulting in +1 frameshift and polypeptide shortening. In contrast to the previous case (T4 DNA topoisomerase mRNA), no pair of matched codons at the borders of the gap, no essential secondary structure, and no stop codon at the border in frame of the gap has been mentioned. Instead, the translation of five specific codons (AUG AGC CAG CGU GAG) preceded by a non-specific sequence longer than 10 codons is required for the jumping. The hypothesis has been put forward that the corresponding sequence of mRNA is specifically looped out in the structure of the mRNA, thus bringing the borders of the by-passed segment into close proximity. It may be assumed that the translating ribosome during translocation can switch over from the ribosome-bound codon to the codon that is spatially adjacent but belongs to the sequence remote along the mRNA chain.

There is a special case when the translating ribosome can hope from one message to another. This

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