Structure and Function of the Stimulatory RNAs Involved in Programmed Eukaryotic –1 Ribosomal Frameshifting (original) (raw)

  1. I. BRIERLEY and
  2. S. PENNELL
  3. Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom

Excerpt

The elongation phase of protein synthesis is of necessity a precise process, and mechanisms exist to promotetranslational fidelity (for review, see Czworkowski andMoore 1996). However, the system must endure a degreeof inaccuracy in order that translation may proceed withsufficient speed. Two major kinds of errors have been described: missense, where an incorrect amino acid is incorporated; and processivity, where premature termination of translation or translational frameshifting occurs(Farabaugh and Bjork 1999). Fortunately, these eventstake place at a relatively low frequency, with frameshifterrors the less common (10-5 per codon; Kurland 1992).A growing number of examples have been described,however, of highly efficient "programmed" frameshiftsites (for review, see Farabaugh 1996, 2000). These ribosomal frameshift signals do not induce "errors" in theclassic sense in that the frameshifts generate authenticproteins, are stimulated by specific elements encoded inthe mRNA, and occur at frequencies that can approach100%. For this reason, they are considered more as extensions of the genetic code (recoding sites; Gesteland etal. 1992; Gesteland and Atkins 1996) rather than "natural" errors, although there may be mechanistic similarities between the two (Farabaugh and Bjork 1999). Thereis considerable interest in how programmed frameshifting occurs, since this may provide insights into normalframe maintenance, tRNA movement, and the unwindingof mRNA secondary structures by ribosomes. This paperfocuses on a particular class of programmed frameshiftsignal, that which directs –1 ribosomal frameshifting,with an emphasis on the stimulatory mRNA elements thatenhance the efficiency of the process. The review concentrates mainly on eukaryotic systems, as prokaryoticframeshifting is discussed elsewhere in this volume...