New & Noteworthy

It Takes More Than an AUG to Translate a Gene

August 2, 2012

Finding genes in this mass of letters will be much simpler if we can predict translation starts. A printout of the human genome presented as a series of books.

Translating a gene is easy, right?  Hop on the end of an mRNA and start translating at the first AUG.

Of course nothing in biology is that simple!  Not all AUGs in the beginning of mRNAs serve as the starts of translation and occasionally translation will start at a codon other than AUG.  There is obviously more to a translation start than an AUG.

In a recent study, Kochetov and coworkers set out to better define what makes a ribosome sit down and start translating.  They used a dataset compiled from S. cerevisiae in 2009 that included a wide range of translation starts ranging from the traditional to the barely recognizable.

The researchers focused on three classes of translation starts:

1)      Traditional yeast gene start sites

2)      AUG-containing uORFs

3)      uORFs that lack an AUG

The last two sets are translation starts that happen upstream of traditional genes (hence the name upstream open reading frame or uORF).  These tend to be weaker than traditional translation starts, have very short associated ORFs, and are thought to play a regulatory role in the translation of the “real” gene.

When Kochetov and coworkers analyzed the data, they confirmed some previous studies that showed that strong translation starts have an AUG, upstream RNA that is predicted to be unfolded and to be A-rich between nucleotides -6 and -1, and downstream RNA that is predicted to form a hairpin.  Most of the traditional yeast genes possessed most of these attributes.  The uORF translation starts were a different matter though.

The uORFs that had an AUG lacked the other features of a strong translation start.  They tended to have fewer A’s in the upstream region and their RNA was structured in all the wrong ways.  The uORFs that lacked an AUG apparently made up for it by having all of the other features of a strong translation start.  They were A-rich between -6 and -1, had an unstructured RNA upstream and a hairpin downstream of the translation start.  The thought is that translation starts that lack an AUG make up for it with all of the rest of the translation context being exceptionally strong. 

These kinds of studies will make the tough job of identifying genes a bit easier.  Which can only be a good thing as more and more genomes come on line.     

How translation worked at Stanford in the 70′s