Study reveals how ribosomes override their blockades

May 14, 2012

Ribosomes are "protein factories" in the cells of all living things. They produce proteins based on existing genetic codes stored on special nucleic acid molecules. These molecules, also called messenger RNA (mRNA) due to the genetic information encoded on them, are read by ribosomes in a stepwise manner. Defined start and stop signals on the mRNA direct this process. If a stop signal is missing, protein formation cannot be completed and the ribosome’s mode of operation is blocked.

Until now, it was not understood in all details how a ribosome can overcome such a blockade. At the center of this repair process, called Trans-Translation, is an additional nucleic acid molecule (tmRNA) that unites characteristics of mRNA and another nucleic acid molecule, the transferRNA (tRNA). The tRNA transfers the correct amino acids to the respective gene sequence on the mRNA during protein biosynthesis. The tmRNA molecule is thus able to smuggle in the missing stop signal and lift the blockade. It was never exactly clear how this large tmRNA molecule moves through the ribosome and smuggles its information into the ribosome’s mRNA channel.

This process could now be documented for the first time using cryo-electron microscopy. This method offers the opportunity to examine the spatial and chronological interaction between individual components of macromolecules. This is done by flash-freezing ribosomes in liquid ethane at -192° Celsius and several hundred-thousand two-dimensional images are projected back into a three-dimensional reconstruction. “With the help of cryo-electron microscopy a unique glimpse of a central key step of the interaction between ribosome, tmRNA, a special protein (SmbP) and the elongation factor G could be attained,” explained David Ramrath, doctoral candidate at the Institute for Medical Physics and Biophysics at Charité and primary author of the study.

The mRNA channel, in which the tmRNA must smuggle the missing information, goes straight through the ribosome’s middle, between the so-called head and body domains of the small ribosomal subunit. Structural analysis showed that cooperation between ribosome and tmRNA in the event of necessary repair is only possible through a change in conformation, that is a short-term and unexpectedly large swivel movement of the ’s head domain.

Explore further: Scientists solve long-standing mystery of protein 'quality control' mechanism

More information: The complex of tmRNA–SmpB and EF-G on translocating ribosomes. David J. F. Ramrath, Hiroshi Yamamoto, Kristian Rother, Daniela Wittek, Markus Pech, Thorsten Mielke, Justus Loerke, Patrick Scheerer, Pavel Ivanov, Yoshika Teraoka, Olga Shpanchenko, Knud H. Nierhaus & Christian M. T. Spahn. Nature (2012), DOI:10.1038/nature11006

Related Stories

A lack of structure facilitates protein synthesis

June 28, 2011

Having an easily accessible starting point on messenger RNA increases protein formation, scientists from the Max Planck Institute of Molecular Plant Physiology in Potsdam have discovered.

Recommended for you

Researchers identify genes for 'Help me!' aromas from corn

October 25, 2016

When corn seedlings are nibbled by caterpillars, they defend themselves by releasing scent compounds that attract parasitic wasps whose larvae consume the caterpillar—but not all corn varieties are equally effective at ...

Genome editing: Efficient CRISPR experiments in mouse cells

October 25, 2016

In order to use the CRISPR-Cas9 system to cut genes, researchers must design an RNA sequence that matches the DNA of the target gene. Most genes have hundreds of such sequences, with varying activity and uniqueness in the ...

Structure of key DNA replication protein solved

October 25, 2016

A research team led by scientists at the Icahn School of Medicine at Mount Sinai (ISMMS) has solved the three-dimensional structure of a key protein that helps damaged cellular DNA repair itself. Investigators say that knowing ...

Microbe hunters discover iron-munching microbe

October 25, 2016

A microbe that 'eats' both methane and iron: microbiologists have long suspected its existence, but were not able to find it - until now. Researchers at Radboud University and the Max Planck Institute for Marine Microbiology ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.