Textbook explanation of mRNA translation may need rethinking

28 Jun 2005

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.

# # #

This press release is based on the following article:

Guanine-nucleotide exchange on ribosome-bound elongation factor G initiates the translocation of tRNAs
Andrey V Zavialov, Vasili V Hauryliuk and Måns Ehrenberg
Journal of Biology 2005, 4:9 (27 June 2005)

Please quote the journal in any story you write, and link to the article if you are writing for the web.

# # #

For further information about this study, contact by e-mail at Måns Ehrenberg ehrenberg@xray.bmc.uu.se

Alternatively, or for more information about the journal, contact Juliette Savin by e-mail at press@biomedcentral.com or by phone on +44 (0)20 7631 9931

# # #

Journal of Biology (http://jbiol.com) is the open access journal for exceptional research. Published by BioMed Central, it provides free access to research articles of the broadest importance and interest. By providing immediate, permanent, unrestricted access to these articles, Journal of Biology ensures the widest possible dissemination of the research it publishes.

BioMed Central (http://www.biomedcentral.com) is an independent online publishing house committed to providing Open Access to peer-reviewed biological and medical research. This commitment is based on the view that immediate free access to research and the ability to freely archive and reuse published information is essential to the rapid and efficient communication of science.

BioMed Central currently publishes over 100 journals across biology and medicine. In addition to open-access original research, BioMed Central also publishes reviews, commentaries and other non-original-research content. Depending on the policies of the individual journal, this content may be open access or provided only to subscribers.