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.

Est3. Plus one frameshifting is required for synthesis of the S. cerevisiae telomerase regulatory subunit Est3 (Ever shorter telomeres 3) (237). A three-protein preassembly complex is present in most of the cell cycle and late in the cycle, after completion of DNA replication, Est3 binds to form active telomerase, which is quickly disassembled by a different pathway. Est3-mediated limitation of the time of formation and quantity of telomerase to a low level may be important for avoidance of telomerase acting at doublestrand breaks where it could prevent repair that would restore genome integrity (238) . The +1 frameshifting occurs at a shift site similar to that of Ty1 just before a UGA terminator at codon 94. trans-frame encoded Est3 is 181 amino acids. The surface of Est3 that interacts with the telomerase RNP pre-assembly complex, the 'TEL' patch is similar to that of mammalian protein TPP1 (239, 240) , and is encoded downstream of the shift site (240) . Under the conditions tested, the frameshift efficiency is high in part due to an 8-fold stimulation by a 3 modular 27-nt stimulatory sequence (237, 241) . Even though a mutation putting the coding sequence into a single frame had no discernible effect on growth in lab media (237) , function is evident because of conservation, including of the 3 stimulator, in diverse budding yeast for 150 million years (242) .