Textbook explanation of mRNA translation may need rethinking
Our understanding of how messenger RNAs are translated into proteins is challenged by new research published today in the Open Access journal Journal of Biology. The study suggests that EF-G, the GTPase that facilitates tRNA translocation in bacteria, enters the ribosome bound to a different guanine nucleotide than previously thought – GDP, not GTP. The ribosome itself then seems to act as the guanine-nucleotide exchange factor, not some as-yet-unidentified factor as previously assumed. This finding questions the prevailing model for RNA translocation.
According to the textbook model EF-G provides the energy needed for the translocation phase of translation by bringing GTP into the ribosome where GTP is subsequently hydrolysed into GDP.
Andrei Zavialov, Vasili Hauryliuk and Måns Ehrenberg from Uppsala University in Sweden first performed an important purification step ensuring that their GTP was not contaminated by GDP (and vice versa), as had been the case with previous studies using these purified components. They next measured the affinity of EF-G for GTP and GDP. Their results strongly suggest that EF-G is bound to GDP in the cytoplasm and that it binds to the pre-translocation complex – composed of the ribosome, tRNA and mRNA strand – as a EF-G-GDP complex. The ribosome itself then seems to act as a GTP exchange factor that swaps GDP for GTP, which results in a modification in the structure of the ribosome. This triggers partial translocation of the mRNA, which is completed after GTP hydrolysis. “Our results suggest that the ribosome plays a previously unidentified dual role of both guanine-nucleotide exchange factor and GTPase-activating protein” explain the authors. EF-G then detaches from the ribosome in its GDP-bound form, ready to be used again by another ribosome.
These findings differ radically from all previous models and as such may represent a considerable step forward in our understanding of translocation, a fundamental mechanism in protein synthesis and gene expression. RNA translation is a highly conserved mechanism and these results using a bacterial system are likely to be applicable to higher organisms as well. This should spur more research in the field to confirm or disprove the findings and give us a clearer picture of RNA translation. In particular, the present clarification of the translocation process at the biochemical level may allow a deeper understanding of how relative movements of the ribosomal subunits can accomplish thousands of translocation events without frame-shifting or loss of tRNA-bound nascent protein chains during peptide elongation.
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