Translation against an applied force

Ribosome structure and mechanism are largely conserved among all known forms of life. Therefore, the motions associated with translation may be among the most ancient and fundamental in biology. However, the molecular mechanism of translocation, the coordinated movement of tRNAs and associated mRNA on the ribosome, has eluded scientists and remains obscure. Single-molecule experiments using optical tweezers and fluorescence microscope are starting to shed new light on these questions. For example, we have observed that moderate forces reverse direction of motion and ribosomes seem to slip backward into the 5' direction along a poly(U) message. Although the detailed molecular mechanism for ribosome slippage is not fully understood, these observations raise interesting biological questions about e.g. -1 frameshifting. Is the -1 frameshift essential for HIV-1 replication a result of tension in the message? Single-molecule experiments open the way towards quantitative modeling of ribosome motion and related phenomena such as -1 frameshifting.