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.

Drosophila lacks telomerase; instead for at least 40 million years, three telomere-specific non-LTR retrotransposons have maintained chromosome ends. One of the three, HeT-A encodes only a Gag-like protein and not its own reverse transcriptase. Nevertheless, this important gag gene requires a frameshifting event for its expression (230, 231) . In another, TART(-B1), the gag termination codon is followed 3 by 37-nt before a +1 frame start codon which is presumed to initiate translation of the polyprotein that includes the reverse transcriptase (232) . As there is a stop codon in the +1 frame in the 37-nt 'spacer', if a GagPol product is synthesized via a tRNA realignment mechanism, it would likely involve bypassing rather than +1 frameshifting, but how the important polyprotein is expressed is unknown. Bypassing was considered as a possibility for synthesis of the counterpart product of mammalian LINE elements. Though only a tiny proportion of those in the human genome are active autonomously, collectively they are important in several ways. They have just three ORFs (233) , with a small number of nucleotides separating the 3 end of ORF1 from the start of ORF2 that encodes an endonuclease and reverse transcriptase activity. However, rather than bypassing being involved in ORF2 expression, some unknown and novel type of initiation, independent of the AUG present, is considered more likely for the curiously stochastic expression involved (234, 235) . In contrast to Drosophila, as described in the section on special characteristics of ciliates and S. cerevisiae, the ciliated protozoan Euplotes has telomeres with frameshifting being required in the synthesis of the telomerase protein La and the reverse transcriptase (TERT) that is the homolog of S. cerevisiae Est2p. In another ciliate, Oxytricha, frameshifting would be required for expression of transposon-derived telomere-bearing elements, whose transposase has been 'domesticated/neofunctionalized' for the genome rearrangement involved in generating socatic macronucleus from germline micronucleus. These elements occupy 13.3% of the micronucleus DNA, and despite the presence of pseudogenes, purifying selection suggests many are expressed (236) .