Mechanism of tRNA-mediated +1 ribosomal frameshifting

Abstract

Significance Accurate gene expression is essential in all organisms. During protein synthesis, transfer RNAs (tRNAs) decode the genetic information contained in messenger RNA (mRNA) on the ribosome into amino acids using a defined 3-nt code. A fundamental question in biology is how the ribosome maintains this 3-nt code, or mRNA frame, during the dynamic processes that move the mRNA-tRNA pairs through the different tRNA-binding sites. We solved structures of a frameshift-prone tRNA bound to the bacterial ribosome after mRNA decoding. We find that the tRNA undergoes conformational rearrangements in the peptidyl (P) and exit (E) sites that cause the ribosome to lose its grip on the mRNA and allow the tRNA to shift into a new reading frame.