Improvement of reading frame maintenance is a common function for several tRNA modifications

Transfer RNAs from all organisms contain many modified nucleosides. Their v astly different chemical structures, their presence in different tRNAs, the ir occurrence in different locations in tRNA and their influence on differe nt reactions in which tRNA participates suggest that each modified nucleosi de may have its own specific function. However, since the frequency of fram eshifting in several different mutants [mnmA, mnmE, tgt, truA (hisT), trmD, miaA, miaB and miaE] defective in tRNA modification was higher compared wi th the corresponding wild-type controls, these modifications have a common function: they all improve reading frame maintenance. Frameshifting occurs by peptidyl-tRNA slippage, which is influenced by the hypomodified tRNA in two ways: (i) a hypomodified tRNA in the ternary complex may decrease the r ate by which the complex is recruited to the A-site and thereby increasing peptidyl-tRNA slippage; or (ii) a hypomodified peptidyl-tRNA may be more pr one to slip than its fully modified counterpart. We propose that the improv ement of reading frame maintenance has been and is the major selective fact or for the emergence of new modified nucleosides.