RNA



Programmed +1 frameshifting stimulated by complementarity between a downstream mRNA sequence and an error-correcting region of rRNA


ZIRONG  LI a1, GUILLAUME  STAHL a1 and PHILIP J.  FARABAUGH a1c1
a1 Department of Biological Sciences and Program in Molecular and Cell Biology, University of Maryland, Baltimore County, Baltimore, Maryland 21250, USA

Abstract

Like most retroviruses and retrotransposons, the retrotransposon Ty3 expresses its pol gene analog (POL3) as a translational fusion to the upstream gag analog (GAG3). The Gag3-Pol3 fusion occurs by frameshifting during translation of the mRNA that encodes the two separate but overlapping ORFs. We showed previously that the shift occurs by out-of-frame binding of a normal aminoacyl-tRNA in the ribosomal A site caused by an aberrant codon•anticodon interaction in the P site. This event is unlike all previously described programmed translational frameshifts because it does not require tRNA slippage between cognate or near-cognate codons in the mRNA. A sequence of 15 nt distal to the frameshift site stimulates frameshifting 7.5-fold. Here we show that the Ty3 stimulator acts as an unstructured region to stimulate frameshifting. Its function depends on strict spacing from the site of frameshifting. Finally, the stimulator increases frameshifting dependent on sense codon-induced pausing, but has no effect on frameshifting dependent on pauses induced by nonsense codons. Complementarity between the stimulator and a portion of the accuracy center of the ribosome, Helix 18, implies that the stimulator may directly disrupt error correction by the ribosome.

(Received September 21 2000)
(Revised October 17 2000)
(Accepted November 7 2000)


Key Words: mRNA-rRNA pairing; recoding; stimulator; translational accuracy.

Correspondence:
c1 Reprint requests to: P.J. Farabaugh, Department of Biological Sciences and Program in Molecular and Cell Biology, University of Maryland, Baltimore County, Baltimore, Maryland 21250, USA; e-mail: farabaug@umbc.edu.