Tuesday, February 26, 2008

A code for translational timing is unravelled by CRG scientists



DNA, mRNA, protein. This is the basic gene expression cycle, and an organisms’ wellbeing depends on its proper regulation in time and space. Scientists at the CRG have recently published in Cell a code that regulates how, when and in which amounts the mRNAs will be translated into proteins.

Some mRNAs – such as those implicated in oocyte maturation or synaptic plasticity – are stored until its time for their translation. There are three signals in the mRNA sequence that determine when it is ready to be translated. The scientists directed by Raúl Méndez have found a code that determines which combinations of these signals establish whether translation activation or repression will occur, as well as how and in which amount the mRNA will be translated.

To do this, they have used frog eggs, in which they studied 5 mRNAs that contained the three signals. By modifying their number and the separation between them they have defined which combinations give rise to which patterns of translational control. This could be confirmed with the help of Roderic Guigó (CRG) through a computational search for genes with these signals. In most cases (> 90%) the translation pattern was shown experimentally to be the one predicted by the new code. They also found that the specific pattern of each gene was conserved across 14 species. Also, using the code, the scientists were able to generate tailor-made translation patterns in synthetic mRNAs. “We are now wondering whether defects in the cellular machinery that reads the code could be implied in pathologies such as cancer”, says Méndez.